Skip to main content
SpringerLink
Log in

Embryonic Stem Cell-Derived Embryoid Bodies: An In Vitro Model of Eutherian Pregastrulation Development and Early Gastrulation

  • Chapter
Stem Cells

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 174))

Abstract

In this review, I describe the dawn of embryoid body research and the influence of stem cell properties on embryoid body development. I will focus on the in vitro differentiation of embryonic stem cells in embryoid bodies. I summarize and combine published data for embryo-like development of embryoid bodies, and based on these findings, I will discuss open questions, concerns, and possible future directions of this still emerging field of research. I hope to provide new perspectives and experimental approaches that go beyond the current state of the art to foster an understanding of eutherian embryogenesis and provide clues for the efficient production of somatic cells for cell therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abe K, Niwa H, Iwase K, Takiguchi M, Mori M, Abe SI, Yamamura KI (1996) Endoderm-specific gene expression in embryonic stem cells differentiated to embryoid bodies. Exp Cell Res 229:27–34

    CAS  PubMed  Google Scholar 

  • Adamson ED, Strickland S, Tu M, Kahan B (1985) A teratocarcinoma-derived endoderm stem cell line (1H5) that can differentiate into extra-embryonic endoderm cell types. Differentiation 29:68–76

    CAS  PubMed  Google Scholar 

  • Allen ND, Barton SC, Hilton K, Norris ML, Surani MA (1994) A functional analysis of imprinting in parthenogenetic embryonic stem cells. Development 120:1473–1482

    CAS  PubMed  Google Scholar 

  • Aumailley M, Pesch M, Tunggal L, Gaill F, Fässler R (2000) Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies. J Cell Sci 113:259–268

    CAS  PubMed  Google Scholar 

  • Bader A, Al-Dubai H, Weitzer G (2000) Leukemia inhibitory factor modulates cardiogenesis in embryoid bodies in opposite fashions. Circ Res 86:787–794

    CAS  PubMed  Google Scholar 

  • Bader A, Gruss A, HÖllrigl A, Al Dubai H, Capetanaki Y, Weitzer G (2001) Paracrine promotion of cardiomyogenesis in embryoid bodies by LIF modulated endoderm. Differentiation 68:31–43

    Article  CAS  PubMed  Google Scholar 

  • Bagutti C, Wobus AM, Fässler R, Watt FM (1996) Differentiation of embryonal stem cells into keratinocytes: comparison of wild-type and beta 1 integrin-deficient cells. Dev Biol 179:184–196

    Article  CAS  PubMed  Google Scholar 

  • Becker S, Wang ZJ, Massey H, Arauz A, Labosky P, Hammerschmidt M, St-Jacques B, Bumcrot D, McMahon A, Grabel L (1997) A role for Indian hedgehog in extraembryonic endoderm differentiation in F9 cells and the early mouse embryo. Dev Biol 187:298–310

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya B, Miura T, Brandenberger R, Mejido J, Luo Y, Yang AX, Joshi BH, Ginis I, Thies RS, Amit M, Lyons I, Condie BG, Itskovitz-Eldor J, Rao MS, Puri RK (2004) Gene expression in human embryonic stem cell lines: unique molecular signature. Blood 103:2956–2964

    Article  CAS  PubMed  Google Scholar 

  • Blewitt ME, Chong S, Whitelaw E (2004) How the mouse got its spots. Trends Genet 20:550–554

    Article  CAS  PubMed  Google Scholar 

  • Boheler KR, Czyz J, Tweedie D, Yang HT, Anisimov SV, Wobus AM (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91:189–201

    Article  CAS  PubMed  Google Scholar 

  • Bradley A, Evans M, Kaufman MH, Robertson E (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255–256

    Article  CAS  PubMed  Google Scholar 

  • Bradley A, Zheng B, Liu P (1998) Thirteen years of manipulating the mouse genome: a personal history. Int J Dev Biol 42:943–950

    CAS  PubMed  Google Scholar 

  • Brand T (2003) Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol 258:1–19

    Article  CAS  PubMed  Google Scholar 

  • Buehr M, Smith A (2003) Genesis of embryonic stem cells. Philos Trans R Soc Lond B Biol Sci 358:1397–1402

    CAS  PubMed  Google Scholar 

  • Buehr M, Nichols J, Stenhouse F, Mountford P, Greenhalgh CJ, Kantachuvesiri S, Brooker G, Mullins J, Smith AG (2003) Rapid loss of Oct-4 and pluripotency in cultured rodent blastocysts and derivative cell lines. Biol Reprod 68:222–229

    CAS  PubMed  Google Scholar 

  • Burdon T, Smith A, Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12:432–438

    Article  CAS  PubMed  Google Scholar 

  • Carpenter MK, Rosler E, Rao MS (2003) Characterization and differentiation of human embryonic stem cells. Cloning Stem Cells 5:79–88

    Article  CAS  PubMed  Google Scholar 

  • Carpenter MK, Rosler ES, Fisk GJ, Brandenberger R, Ares X, Miura T, Lucero M, Rao MS (2004) Properties of four human embryonic stem cell lines maintained in a feeder-free culture system. Dev Dyn 229:243–258

    Article  CAS  PubMed  Google Scholar 

  • Casanova JE, Grabel LB (1988) The role of cell interactions in the differentiation of teratocarcinoma-derived parietal and visceral endoderm. Dev Biol 129:124–139

    Article  CAS  PubMed  Google Scholar 

  • Chambers I, Smith A (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23:7150–7160

    Article  CAS  PubMed  Google Scholar 

  • Chang IK, Jeong DK, Hong YH, Park TS, Moon YK, Ohno T, Han JY (1997) Production of germline chimeric chickens by transfer of cultured primordial germ cells. Cell Biol Int 21:495–499

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Li H (2004) [Progress in the studies of parthenogenetic embryonic stem cells]. Zhonghua Nan Ke Xue 10:55–58

    CAS  PubMed  Google Scholar 

  • Chen Y, Li X, Eswarakumar VP, Seger R, Lonai P (2000) Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation. Oncogene 19:3750–3756

    Article  CAS  PubMed  Google Scholar 

  • Cheng L, Grabel LB (1997) The involvement of tissue-type plasminogen activator in parietal endoderm outgrowth. Exp Cell Res 230:187–196

    Article  CAS  PubMed  Google Scholar 

  • Chong S, Whitelaw E (2004) Epigenetic germline inheritance. Curr Opin Genet Dev 14:692–696

    Article  CAS  PubMed  Google Scholar 

  • Conley BJ, Trounson AO, Mollard R (2004a) Human embryonic stem cells form embryoid bodies containing visceral endoderm-like derivatives. Fetal Diagn Ther 19:218–223

    Article  PubMed  Google Scholar 

  • Conley BJ, Young JC, Trounson AO, Mollard R (2004b) Derivation, propagation and differentiation of human embryonic stem cells. Int J Biochem Cell Biol 36:555–567

    Article  CAS  PubMed  Google Scholar 

  • Coucouvanis E, Martin GR (1999) BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. Development 126:535–546

    CAS  PubMed  Google Scholar 

  • Czyz J, Wobus A (2001) Embryonic stem cell differentiation: the role of extracellular factors. Differentiation 68:167–174

    Article  CAS  PubMed  Google Scholar 

  • Czyz J, Wiese C, Rolletschek A, Blyszczuk P, Cross M, Wobus AM (2003) Potential of embryonic and adult stem cells in vitro. Biol Chem 384:1391–1409

    Article  CAS  PubMed  Google Scholar 

  • Daley GQ (2003) From embryos to embryoid bodies: generating blood from embryonic stem cells. Ann N Y Acad Sci 996:122–131

    PubMed  Google Scholar 

  • Dang SM, Zandstra PW (2004) Scalable production of embryonic stem cell-derived cells. Methods Mol Biol 290:353–364

    Google Scholar 

  • Dang SM, Kyba M, Perlingeiro R, Daley GQ, Zandstra PW (2002) Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems. Biotechnol Bioeng 78:442–453

    Article  CAS  PubMed  Google Scholar 

  • Dang SM, Gerecht-Nir S, Chen J, Itskovitz-Eldor J, Zandstra PW (2004) Controlled, scalable embryonic stem cell differentiation culture. Stem Cells 22:275–282

    Article  PubMed  Google Scholar 

  • Dean W, Santos F, Reik W (2003) Epigenetic reprogramming in early mammalian development and following somatic nuclear transfer. Semin Cell Dev Biol 14:93–100

    Article  CAS  PubMed  Google Scholar 

  • Desbaillets I, Ziegler U, Groscurth P, Gassmann M (2000) Embryoid bodies: an in vitro model of mouse embryogenesis. Exp Physiol 85:645–651

    Article  CAS  PubMed  Google Scholar 

  • Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet 19:348–355

    PubMed  Google Scholar 

  • Doetschman TC, Eistetter H, Katz M, Schmidt W, Kemler R (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol 87:27–45

    CAS  PubMed  Google Scholar 

  • Doetschman T, Williams P, Maeda N (1988) Establishment of hamster blastocyst-derived embryonic stem (ES) cells. Dev Biol 127:224–227

    Article  CAS  PubMed  Google Scholar 

  • Dyban PA (1984) [Characteristics of the growth and differentiation of teratocarcinoma OC15S1 in syngeneic and allogeneic mice]. Biull Eksp Biol Med 97:71–72

    CAS  PubMed  Google Scholar 

  • Edwards RG (2004) Stem cells today: A. Origin and potential of embryo stem cells. Reprod Biomed Online 8:275–306

    CAS  PubMed  Google Scholar 

  • Esner M, Pachernik J, Hampl A, Dvorak P (2002) Targeted disruption of fibroblast growth factor receptor-1 blocks maturation of visceral endoderm and cavitation in mouse embryoid bodies. Int J Dev Biol 46:817–825

    CAS  PubMed  Google Scholar 

  • Evans MJ (1972) The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratoma cells. J Embryol Exp Morphol 28:163–176

    CAS  PubMed  Google Scholar 

  • Evans M (1981) Origin of mouse embryonal carcinoma cells and the possibility of their direct isolation into tissue culture. J Reprod Fertil 62:625–631

    CAS  PubMed  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    CAS  PubMed  Google Scholar 

  • Fässler R, Pfaff M, Murphy J, Noegel AA, Johansson S, Timpl R, Albrecht R (1995) Lack of beta 1 integringene in embryonic stem cells affects morphology, adhesion, and migration but not integration into the inner cell mass of blastocysts. J Cell Biol 128:979–988

    PubMed  Google Scholar 

  • Fässler R, Rohwedel J, Maltsev V, Bloch W, Lentini S, Guan K, Gullberg D, Hescheler J, Addicks K, Wobus AM (1996) Differentiation and integrity of cardiac muscle cells are impaired in the absence of beta 1 integrin. J Cell Sci 109:2989–2999

    PubMed  Google Scholar 

  • Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA, Hatzfeld A, Usta F, Vega VB, Long PM, Libermann TA, Lim B (2003) Comment on “’stemness’: transcriptional profiling of embryonic and adult stem cells” and “a stem cell molecular signature”. Science 302:393b

    Article  CAS  PubMed  Google Scholar 

  • Fujikura J, Yamato E, Yonemura S, Hosoda K, Masui S, Nakao K, Miyazaki Ji J, Niwa H (2002) Differentiation of embryonic stem cells is induced by GATA factors. Genes Dev 16:784–789

    Article  CAS  PubMed  Google Scholar 

  • Gao F, Shi HY, Daughty C, Cella N, Zhang M (2004) Maspin plays an essential role in early embryonic development. Development 131:1479–1489

    Article  CAS  PubMed  Google Scholar 

  • Gardner RL (1985) Regeneration of endoderm from primitive ectoderm in the mouse embryo: fact or artifact? J Embryol Exp Morphol 88:303–326

    CAS  PubMed  Google Scholar 

  • Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, Daley GQ (2004) Derivation of embryonic germ cells and male gametes from embryonic stemcells. Nature 427:148–154

    Article  CAS  PubMed  Google Scholar 

  • Gerecht-Nir S, Cohen S, Itskovitz-Eldor J (2004) Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation. Biotechnol Bioeng 86:493–502

    Article  CAS  PubMed  Google Scholar 

  • Ginis I, Luo Y, Miura T, Thies S, Brandenberger R, Gerecht-Nir S, Amit M, Hoke A, Carpenter MK, Itskovitz-Eldor J, Rao MS (2004) Differences between human and mouse embryonic stem cells. Dev Biol 269:360–380

    Article  CAS  PubMed  Google Scholar 

  • Grabel LB, Casanova JE (1986) The outgrowth of parietal endoderm from mouse teratocarcinoma stem-cell embryoid bodies. Differentiation 32:67–73

    CAS  PubMed  Google Scholar 

  • Grabel LB, Watts TD (1987) The role of extracellular matrix in the migration and differentiation of parietal endoderm from teratocarcinoma embryoid bodies. J Cell Biol 105:441–448

    Article  CAS  PubMed  Google Scholar 

  • Graves KH, Moreadith RW (1993) Derivation and characterization of putative pluripotential embryonic stemcells from preimplantation rabbit embryos. Mol Reprod Dev 36:424–433

    Article  CAS  PubMed  Google Scholar 

  • Grover A, Oshima RG, Adamson ED (1983) Epithelial layer formation in differentiating aggregates of F9 embryonal carcinoma cells. J Cell Biol 96:1690–1696

    Article  CAS  PubMed  Google Scholar 

  • Hamazaki T, Oka M, Yamanaka S, Terada N (2004) Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation. J Cell Sci 117:5681–5686

    Article  CAS  PubMed  Google Scholar 

  • Harland R, Gerhart J (1997) Formation and function of Spemann’s organizer. Annu Rev Cell Dev Biol 13:611–667

    Article  CAS  PubMed  Google Scholar 

  • Hescheler J, Fleischmann BK, Lentini S, Maltsev VA, Rohwedel J, Wobus AM, Addicks K (1997) Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis. Cardiovasc Res 36:149–162

    Article  CAS  PubMed  Google Scholar 

  • Hochepied T, Schoonjans L, Staelens J, Kreemers V, Danloy S, Puimege L, Collen D, Van Roy F, Libert C (2004) Breaking the species barrier: derivation of germline-competent embryonic stem cells from Mus spretus x C57BL/6 hybrids. Stem Cells 22:441–447

    Article  PubMed  Google Scholar 

  • Hong Y, Winkler C, Schartl M (1998a) Efficiency of cell culture derivation from blastula embryos and of chimera formation in the medaka (Oryzias latipes) depends on donor genotype and passage number. Dev Genes Evol 208:595–602

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Winkler C, Schartl M (1998b) Production of medakafish chimeras from a stable embryonic stem cell line. Proc Natl Acad Sci U S A 95:3679–3684

    Article  CAS  PubMed  Google Scholar 

  • Hubner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss JF 3rd, Boiani M, Scholer HR (2003) Derivation of oocytes from mouse embryonic stem cells. Science 300:1251–1256

    Article  PubMed  Google Scholar 

  • Humphrey RK, Beattie GM, Lopez AD, Bucay N, King CC, Firpo MT, Rose-John S, Hayek A (2004) Maintenance of pluripotency in human embryonic stem cells is STAT3 independent. Stem Cells 22:522–530

    Article  CAS  PubMed  Google Scholar 

  • Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM 3rd, Biniszkiewicz D, Yanagimachi R, Jaenisch R (2001) Epigenetic instability in ES cells and cloned mice. Science 293:95–97

    Article  CAS  PubMed  Google Scholar 

  • Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM, Jeon HY, Lee BC, Kang SK, Kim SJ, Ahn C, Hwang JH, Park KY, Cibelli JB, Moon SY (2004) Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 303:1669–1674

    Article  CAS  PubMed  Google Scholar 

  • Iannaccone PM, Taborn GU, Garton RL, Caplice MD, Brenin DR (1994) Pluripotent embryonic stem cells from the rat are capable of producing chimeras. Dev Biol 163:288–292

    Article  CAS  PubMed  Google Scholar 

  • Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, Togawa A, Takahashi K, Nishioka H, Yoshida H, Mizoguchi A, Nishikawa S, Takai Y (1999) Afadin: a key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol 146:1117–1131

    Article  CAS  PubMed  Google Scholar 

  • Itskovitz Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N (2000) Differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers. Mol Med 6:88–95

    CAS  PubMed  Google Scholar 

  • Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stemcell molecular signature. Science 298:601–604

    Article  CAS  PubMed  Google Scholar 

  • Jiang R, Grabel LB (1995) Function and differential regulation of the alpha 6 integrin isoforms during parietal endoderm differentiation. Exp Cell Res 217:195–204

    Article  CAS  PubMed  Google Scholar 

  • Jiang R, Kato M, Bernfield M, Grabel LB (1995) Expression of syndecan-1 changes during the differentiation of visceral and parietal endoderm from murine F9 teratocarcinoma cells. Differentiation 59:225–233

    Article  CAS  PubMed  Google Scholar 

  • Kaufman MH, Robertson EJ, Handyside AH, Evans MJ (1983) Establishment of pluripotential cell lines from haploid mouse embryos. J Embryol Exp Morphol 73:249–261

    CAS  PubMed  Google Scholar 

  • Keller G, Kennedy M, Papayannopoulou T, Wiles MV (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 13:473–486

    CAS  PubMed  Google Scholar 

  • Keller R, Davidson LA, Shook DR (2003) How we are shaped: the biomechanics of gastrulation. Differentiation 71:171–205

    Article  PubMed  Google Scholar 

  • Kleinsmith LJ, Pierce GB Jr (1964) Multipotentiality of single embryonal carcinoma cells. Cancer Res 24:1544–1551

    CAS  PubMed  Google Scholar 

  • Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M, Woo S, Fehling HJ, Keller G (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131:1651–1662

    Article  CAS  PubMed  Google Scholar 

  • Kuo HC, Pau KY, Yeoman RR, Mitalipov SM, Okano H, Wolf DP (2003) Differentiation of monkey embryonic stem cells into neural lineages. Biol Reprod 68:1727–1735

    CAS  PubMed  Google Scholar 

  • Lacham-Kaplan O (2004) In vivo and in vitro differentiation of male germ cells in the mouse. Reproduction 128:147–152

    Article  PubMed  Google Scholar 

  • Lake J, Rathjen J, Remiszewski J, Rathjen PD (2000) Reversible programming of pluripotent cell differentiation. J Cell Sci 113:555–566

    CAS  PubMed  Google Scholar 

  • Lang KJ, Rathjen J, Vassilieva S, Rathjen PD (2004) Differentiation of embryonic stem cells to a neural fate: a route to re-building the nervous system? J Neurosci Res 76:184–192

    Article  CAS  PubMed  Google Scholar 

  • Lanza R (2004a) Handbook of stem cells. Elsevier, Academic Press, Amsterdam

    Google Scholar 

  • Lanza R (2004b) Handbook of stem cells. Elsevier, Academic Press, Amsterdam

    Google Scholar 

  • Lauss M, Stary M, Tischler J, Egger G, Puz S, Bader-Allmer A, Seiser C, Weitzer G (2005) Single inner cell masses yield embryonic stem cell lines differing in life expression and their developmental potential. Biochem Biophys Res Commun 331:1577–1586

    Article  CAS  PubMed  Google Scholar 

  • Lavon N, Benvenisty N (2003) Differentiation and genetic manipulation of human embryonic stem cells and the analysis of the cardiovascular system. Trends Cardiovasc Med 13:47–52

    Article  CAS  PubMed  Google Scholar 

  • Leahy A, Xiong JW, Kuhnert F, Stuhlmann H (1999) Use of developmental marker genes to define temporal and spatial patterns of differentiation during embryoid body formation. J Exp Zool 284:67–81

    Article  CAS  PubMed  Google Scholar 

  • Levine AJ, Torosian M, Sarokhan AJ, Teresky AK (1974) Biochemical criteria for the in vitro differentiation of embryoid bodies produced by a transplantable teratoma of mice. The production of acetylcholine esterase and creatine phosphokinase by teratomacells. J Cell Physiol 84:311–317

    CAS  PubMed  Google Scholar 

  • Li L, Arman E, Ekblom P, Edgar D, Murray P, Lonai P (2004) Distinct GATA6-and laminin-dependent mechanisms regulate endodermal and ectodermal embryonic stemcell fates. Development 131:5277–5286

    CAS  PubMed  Google Scholar 

  • Li M, Pevny L, Lovell Badge R, Smith A (1998) Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr Biol 8:971–974

    Article  CAS  PubMed  Google Scholar 

  • Li S, Harrison D, Carbonetto S, Fassler R, Smyth N, Edgar D, Yurchenco PD (2002) Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation. J Cell Biol 157:1279–1290

    CAS  PubMed  Google Scholar 

  • Li M, Zhang D, Hou Y, Jiao L, Zheng X, Wang WH (2003a) Isolation and culture of embryonic stem cells from porcine blastocysts. Mol Reprod Dev 65:429–434

    Article  CAS  PubMed  Google Scholar 

  • Li S, Edgar D, Fassler R, Wadsworth W, Yurchenco PD (2003b) The role of laminin in embryonic cell polarization and tissue organization. Dev Cell 4:613–624

    CAS  PubMed  Google Scholar 

  • Li X, Chen Y, Scheele S, Arman E, Haffner Krausz R, Ekblom P, Lonai P (2001) Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body. J Cell Biol 153:811–822

    Article  CAS  PubMed  Google Scholar 

  • Maltsev VA, Rohwedel J, Hescheler J, Wobus AM (1993) Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Mech Dev 44:41–50

    Article  CAS  PubMed  Google Scholar 

  • Mann JR, Gadi I, Harbison ML, Abbondanzo SJ, Stewart CL (1990) Androgenetic mouse embryonic stem cells are pluripotent and cause skeletal defects in chimeras: implications for genetic imprinting. Cell 62:251–260

    Article  CAS  PubMed  Google Scholar 

  • Martin GR (1980) Teratocarcinomas and mammalian embryogenesis. Science 209:768–776

    CAS  PubMed  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    CAS  PubMed  Google Scholar 

  • Martin GR, Evans MJ (1975) Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proc Natl Acad Sci U S A 72:1441–1445

    CAS  PubMed  Google Scholar 

  • Martin GR, Wiley LM, Damjanov I (1977) The development of cystic embryoid bodies in vitro from clonal teratocarcinoma stem cells. Dev Biol 61:230–244

    Article  CAS  PubMed  Google Scholar 

  • Masson P (1970) Human tumors, histology, diagnosis and technique, http://www.navi.net/~rsc/cancer/masson01.txt edn. Wayne State University Press

    Google Scholar 

  • Matsui Y, Zsebo K, Hogan BL (1992) Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70:841–847

    Article  CAS  PubMed  Google Scholar 

  • McBurney MW, Strutt BJ (1980) Genetic activity of X chromosomes in pluripotent female teratocarcinoma cells and their differentiated progeny. Cell 21:357–364

    Article  CAS  PubMed  Google Scholar 

  • Miki K (1999) Volume of liquid below the epithelium of an F9 cell as a signal for differentiation into visceral endoderm. J Cell Sci 112:3071–3080

    CAS  PubMed  Google Scholar 

  • Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134:1255–1270

    Article  CAS  PubMed  Google Scholar 

  • Mitalipova M, Beyhan Z, First NL (2001) Pluripotency of bovine embryonic cell line derived from precompacting embryos. Cloning 3:59–67

    Article  CAS  PubMed  Google Scholar 

  • Moens A, Flechon B, Degrouard J, Vignon X, Ding J, Flechon JE, Betteridge KJ, Renard JP (1997) Ultrastructural and immunocytochemical analysis of diploid germ cells isolated from fetal rabbit gonads. Zygote 5:47–60

    CAS  PubMed  Google Scholar 

  • Mummery CL, van den Eijnden-van Raaij AJ, Feijen A, Freund E, Hulskotte E, Schoorlemmer J, Kruijer W (1990) Expression of growth factors during the differentiation of embryonic stem cells in monolayer. Dev Biol 142:406–413

    CAS  PubMed  Google Scholar 

  • Mummery CL, van Achterberg TA, van den Eijnden-van Raaij AJ, van Haaster L, Willemse A, de Laat SW, Piersma AH (1991) Visceral-endoderm-like cell lines induce differentiation of murine P19 embryonal carcinoma cells. Differentiation 46:51–60

    CAS  PubMed  Google Scholar 

  • Murray P, Edgar D (2001a) The regulation of embryonic stem cell differentiation by leukaemia inhibitory factor (LIF). Differentiation 68:227–234

    Article  CAS  PubMed  Google Scholar 

  • Murray P, Edgar D (2001b) Regulation of the differentiation and behaviour of extraembryonic endodermal cells by basement membranes. J Cell Sci 114:931–939

    CAS  PubMed  Google Scholar 

  • Murray P, Edgar D (2004) The topographical regulation of embryonic stem cell differentiation. Philos Trans R Soc Lond B Biol Sci 359:1009–1020

    CAS  PubMed  Google Scholar 

  • Nakatsuji N, Suemori H (2002) Embryonic stem cell lines of nonhuman primates. Sci World J 2:1762–1773

    Google Scholar 

  • Nicolas JF, Dubois P, Jakob H, Gaillard J, Jacob F (1975) [Mouse teratocarcinoma: differentiation in cultures of a multipotential primitive cell line (author’s transl)]. Ann Microbiol (Paris) 126:3–22

    CAS  Google Scholar 

  • Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24:372–376

    Article  CAS  PubMed  Google Scholar 

  • Notarianni E, Galli C, Laurie S, Moor RM, Evans MJ (1991) Derivation of pluripotent, embryonic cell lines from the pig and sheep. J Reprod Fertil Suppl 43:255–260

    CAS  Google Scholar 

  • Nusslein-Volhard CN (2004) Von Genen und Embryonen. Reclam Verlag, Leipzig

    Google Scholar 

  • O’shea KS(2004) Self-renewal vs. differentiation of mouse embryonic stem cells. Biol Reprod 71:1755–1765

    Google Scholar 

  • Pain B, Clark ME, Shen M, Nakazawa H, Sakurai M, Samarut J, Etches RJ (1996) Long-term in vitro culture and characterisation of avian embryonic stem cells with multiple morphogenetic potentialities. Development 122:2339–2348

    CAS  PubMed  Google Scholar 

  • Pandur P, Lasche M, Eisenberg LM, Kuhl M (2002) Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418:636–641

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Kim SJ, Lee JB, Song JM, Kim CG, Roh S 2nd, Yoon HS (2004) Establishment of a human embryonic germ cell line and comparison with mouse and human embryonic stem cells. Mol Cells 17:309–315

    CAS  PubMed  Google Scholar 

  • Pau KY, Wolf DP (2004) Derivation and characterization of monkey embryonic stem cells. Reprod Biol Endocrinol 2:41

    Article  PubMed  Google Scholar 

  • Pelton TA, Bettess MD, Lake J, Rathjen J, Rathjen PD (1998) Developmental complexity of early mammalian pluripotent cell populations in vivo and in vitro. Reprod Fertil Dev 10:535–549

    Article  CAS  PubMed  Google Scholar 

  • Pesce M, Scholer HR (2001) Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19:271–278

    Article  CAS  PubMed  Google Scholar 

  • Petitte JN, Liu G, Yang Z (2004) Avian pluripotent stem cells. Mech Dev 121:1159–1168

    Article  CAS  PubMed  Google Scholar 

  • Peyron A (1939) Faits nouveaux relatifs à l’origine et à l’histogénèse des embryomes. Bull Assoc Franc étude cancer 28:658–681

    Google Scholar 

  • Piedrahita JA, Moore K, Oetama B, Lee CK, Scales N, Ramsoondar J, Bazer FW, Ott T (1998) Generation of transgenic porcine chimeras using primordial germ cell-derived colonies. Biol Reprod 58:1321–1329

    Article  CAS  PubMed  Google Scholar 

  • Pierce GB Jr, Dixon FJ Jr, Verney EL (1960) Teratocarcinogenic and tissue-forming potentials of the cell types comprising neoplastic embryoid bodies. Lab Invest 9:583–602

    PubMed  Google Scholar 

  • Prelle K, Zink N, Wolf E (2002) Pluripotent stem cells—model of embryonic development, tool for gene targeting, and basis of cell therapy. Anat Histol Embryol 31:169–186

    PubMed  Google Scholar 

  • Rakyan VK, Preis J, Morgan HD, Whitelaw E (2001) The marks, mechanisms and memory of epigenetic states in mammals. Biochem J 356:1–10

    Article  CAS  PubMed  Google Scholar 

  • Ramalho Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298:597–600

    CAS  PubMed  Google Scholar 

  • Rathjen J, Rathjen PD (2003) Lineage specific differentiation of mouse ES cells: formation and differentiation of early primitive ectoderm-like (EPL) cells. Methods Enzymol 365:3–25

    PubMed  Google Scholar 

  • Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    Article  CAS  PubMed  Google Scholar 

  • Resnick JL, Bixler LS, Cheng L, Donovan PJ (1992) Long-term proliferation of mouse primordial germ cells in culture. Nature 359:550–551

    Article  CAS  PubMed  Google Scholar 

  • Robertson EJ, Evans MJ, Kaufman MH (1983) X-chromosome instability in pluripotential stem cell lines derived from parthenogenetic embryos. J Embryol Exp Morphol 74:297–309

    CAS  PubMed  Google Scholar 

  • Robertson E, Bradley A, Kuehn M, Evans M (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323:445–448

    Article  CAS  PubMed  Google Scholar 

  • Robertson EJ, Conlon FL, Barth KS, Costantini F, Lee JJ (1992) Use of embryonic stem cells to study mutations affecting postimplantation development in the mouse. Ciba Found Symp 165:237–250; discussion 250–255

    CAS  PubMed  Google Scholar 

  • Rohwedel J, Guan K, Zuschratter W, Jin S, Ahnert-Hilger G, Furst D, Fassler R, Wobus AM (1998) Loss of beta1 integrin function results in a retardation of myogenic, but an acceleration of neuronal, differentiation of embryonic stem cells in vitro. Dev Biol 201:167–184

    Article  CAS  PubMed  Google Scholar 

  • Rossant J (2001) Stem cells from the mammalian blastocyst. Stem Cells 19:477–482

    Article  CAS  PubMed  Google Scholar 

  • Rossant J, Tam PPL (2002) Mouse development. Academic Press, London

    Google Scholar 

  • Sachinidis A, Fleischmann BK, Kolossov E, Wartenberg M, Sauer H, Hescheler J (2003) Cardiac specific differentiation of mouse embryonic stem cells. Cardiovasc Res 58:278–291

    Article  CAS  PubMed  Google Scholar 

  • Saito S, Ugai H, Sawai K, Yamamoto Y, Minamihashi A, Kurosaka K, Kobayashi Y, Murata T, Obata Y, Yokoyama K (2002) Isolation of embryonic stem-like cells from equine blastocysts and their differentiation in vitro. FEBS Lett 531:389–396

    Article  CAS  PubMed  Google Scholar 

  • Sato N, Sanjuan IM, Heke M, Uchida M, Naef F, Brivanlou AH (2003)Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 260:404–413

    Article  CAS  PubMed  Google Scholar 

  • Schoonjans L, Albright GM, Li JL, Collen D, Moreadith RW (1996) Pluripotential rabbit embryonic stem (ES) cells are capable of forming overt coat color chimeras following injection into blastocysts. Mol Reprod Dev 45:439–443

    Article  CAS  PubMed  Google Scholar 

  • Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 97:11307–11312

    Article  CAS  PubMed  Google Scholar 

  • Schultheiss TM, Burch JB, Lassar AB (1997) A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 11:451–462

    CAS  PubMed  Google Scholar 

  • Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci U S A 95:13726–13731

    Article  CAS  PubMed  Google Scholar 

  • Shim H, Gutierrez-Adan A, Chen LR, BonDurant RH, Behboodi E, Anderson GB (1997) Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Biol Reprod 57:1089–1095

    Article  CAS  PubMed  Google Scholar 

  • Smith A (2001a) Embryonic stem cells. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • Smith AG (2001b) Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435–462

    Article  CAS  PubMed  Google Scholar 

  • Smith ER, Smedberg JL, Rula ME, Xu XX (2004) Regulation of Ras-MAPK pathway mitogenic activity by restricting nuclear entry of activated MAPK in endoderm differentiation of embryonic carcinoma and stem cells. J Cell Biol 164:689–699

    Article  CAS  PubMed  Google Scholar 

  • Smith JC, Gurdon JB (2004) Many ways to make a gradient. Bioessays 26:705–706

    CAS  PubMed  Google Scholar 

  • Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, Edgar D (1999) Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol 144:151–160

    Article  CAS  PubMed  Google Scholar 

  • Soriano P, Montgomery C, Geske R, Bradley A (1991) Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64:693–702

    Article  CAS  PubMed  Google Scholar 

  • Soudais C, Bielinska M, Heikinheimo M, MacArthur CA, Narita N, Saffitz JE, Simon MC, Leiden JM, Wilson DB (1995) Targeted mutagenesis of the transcription factor GATA-4 gene in mouse embryonic stem cells disrupts visceral endoderm differentiation in vitro. Development 121:3877–3888

    CAS  PubMed  Google Scholar 

  • Stern CD, Canning DR (1990) Origin of cells giving rise to mesoderm and endoderm in chick embryo. Nature 343:273–275

    Article  CAS  PubMed  Google Scholar 

  • Stevens LC (1958) Studies on transplantable testicular teratomas of strain 129 mice. J Natl Cancer Inst 20:1257–1275

    CAS  PubMed  Google Scholar 

  • Stevens LC (1959) Embryology of testicular teratomas in strain 129 mice. J Natl Cancer Inst 23:1249–1295

    CAS  PubMed  Google Scholar 

  • Stevens LC (1960) Embryonic potency of embryoid bodies derived from a transplantable testicular teratoma of the mouse. Dev Biol 2:285–297

    Article  CAS  PubMed  Google Scholar 

  • Stice SL, Strelchenko NS, Keefer CL, Matthews L (1996) Pluripotent bovine embryonic cell lines direct embryonic development following nuclear transfer. Biol Reprod 54:100–110

    Article  CAS  PubMed  Google Scholar 

  • Suemori H, Nakatsuji N (2003) Growth and differentiation of cynomolgus monkey ES cells. Methods Enzymol 365:419–429

    PubMed  Google Scholar 

  • Sukoyan MA, Golubitsa AN, Zhelezova AI, Shilov AG, Vatolin SY, Maximovsky LP, Andreeva LE, McWhir J, Pack SD, Bayborodin SI (1992) Isolation and cultivation of blastocyst-derived stem cell lines from American mink (Mustela vison). Mol Reprod Dev 33:418–431

    Article  CAS  PubMed  Google Scholar 

  • Sukoyan MA, Vatolin SY, Golubitsa AN, Zhelezova AI, Semenova LA, Serov OL (1993) Embryonic stem cells derived from morulae, inner cell mass, and blastocysts of mink: comparisons of their pluripotencies. Mol Reprod Dev 36:148–158

    Article  CAS  PubMed  Google Scholar 

  • Tanaka S, Kunath T, Hadjantonakis AK, Nagy A, Rossant J (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282:2072–2075

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Marshall VS (1998) Primate embryonic stem cells. Curr Top Dev Biol 38:133–165

    CAS  PubMed  Google Scholar 

  • Thompson JR, Gudas LJ (2002) Retinoic acid induces parietal endoderm but not primitive endoderm and visceral endoderm differentiation in F9 teratocarcinoma stem cells with a targeted deletion of the Rex-1 (Zfp-42) gene. Mol Cell Endocrinol 195:119–133

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP (1995) Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci U S A 92:7844–7848

    CAS  PubMed  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Hearn JP (1996) Pluripotent cell lines derived from common marmoset (Callithrix jacchus) blastocysts. Biol Reprod 55:254–259

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Vallier L, Reynolds D, Pedersen RA (2004) Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway. Dev Biol 275:403–421

    Article  CAS  PubMed  Google Scholar 

  • Veltmaat JM, Orelio CC, Ward Van Oostwaard D, Van Rooijen MA, Mummery CL, Defize LH (2000) Snail is an immediate early target gene of parathyroid hormone related peptide signaling in parietal endoderm formation. Int J Dev Biol 44:297–307

    CAS  PubMed  Google Scholar 

  • Verheijen MH, Defize LH (1999) Signals governing extraembryonic endoderm formation in the mouse: involvement of the type 1 parathyroid hormone-related peptide (PTHrP) receptor, p21Ras and cell adhesion molecules. Int J Dev Biol 43:711–721

    CAS  PubMed  Google Scholar 

  • Wang QT, Piotrowska K, Ciemerych MA, Milenkovic L, Scott MP, Davis RW, Zernicka-Goetz M (2004) A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell 6:133–144

    Article  CAS  PubMed  Google Scholar 

  • Watson AJ, Barcroft LC (2001) Regulation of blastocyst formation. Front Biosci 6: D708–D730

    CAS  PubMed  Google Scholar 

  • Weitzer G, Milner DJ, Kim JU, Bradley A, Capetanaki Y (1995) Cytoskeletal control of myogenesis: a desmin null mutation blocks the myogenic pathway during embryonic stem cell differentiation. Dev Biol 172:422–439

    Article  CAS  PubMed  Google Scholar 

  • Wells DN, Misica PM, Day TA, Tervit HR (1997) Production of cloned lambs from an established embryonic cell line: a comparison between in vivo-and in vitro-matured cytoplasts. Biol Reprod 57:385–393

    Article  CAS  PubMed  Google Scholar 

  • Wheeler MB (1994) Development and validation of swine embryonic stem cells: a review. Reprod Fertil Dev 6:563–568

    Article  CAS  PubMed  Google Scholar 

  • Wobus AM, Boheler KR (2005) Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 85:635–678

    Article  CAS  PubMed  Google Scholar 

  • Wobus AM, Rohwedel J, Strübing C, Jin S, Adler K, Maltsev V, Hescheler J (1997) In vitro differentiation of embryonic stem cells. Blackwell, Berlin, pp 1–17

    Google Scholar 

  • Xiong JW, Battaglino R, Leahy A, Stuhlmann H (1998) Large-scale screening for developmental genes in embryonic stem cells and embryoid bodies using retroviral entrapment vectors. Dev Dyn 212:181–197

    Article  CAS  PubMed  Google Scholar 

  • Xu RH, Chen X, Li DS, Li R, Addicks GC, Glennon C, Zwaka TP, Thomson JA (2002) BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol 20:1261–1264

    Article  CAS  PubMed  Google Scholar 

  • Yoshida-Koide U, Matsuda T, Saikawa K, Nakanuma Y, Yokota T, Asashima M, Koide H (2004) Involvement of Ras in extraembryonic endoderm differentiation of embryonic stem cells. Biochem Biophys Res Commun 313:475–481

    Article  CAS  PubMed  Google Scholar 

  • Young RH (2004) A brief history of the pathology of the gonads. Mod Pathol doi:10.1038/modpathol.3800305:1–15

    Google Scholar 

  • Yu L, Sangster N, Perez A, McCormick PJ (2004) The bHLH protein MyoR inhibits the differentiation of early embryonic endoderm. Differentiation 72:341–347

    Article  CAS  PubMed  Google Scholar 

  • Zeng X, Miura T, Luo Y, Bhattacharya B, Condie B, Chen J, Ginis I, Lyons I, Mejido J, Puri RK, Rao MS, Freed WJ (2004) Properties of pluripotent human embryonic stem cells BG01 and BG02. Stem Cells 22:292–312

    CAS  PubMed  Google Scholar 

  • Zeuthen J, Norgaard JO, Avner P, Fellous M, Wartiovaara J, Vaheri A, Rosen A, Giovanella BC (1980) Characterization of a human ovarian teratocarcinoma-derived cell line. Int J Cancer 25:19–32

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max F. Perutz Laboratories, Department of Medical Biochemistry, Division of Molecular Cell Biology, University Institutes at the Vienna Biocenter, Medical University of Vienna, Dr. Bohrgasse 9, 1030, Vienna, Austria

    G. Weitzer

Authors
  1. G. Weitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. In Vitro Differentiation Group, Dept. of Cytogenetics, Leibnitz Institute of Plant Genetics and Crop Plant Research (IPK), Corrensstr. 3, D-06466, Gatersleben, Germany

    Anna M. Wobus PhD

  2. Laboratory of Cardiovascular Science, Gerontology Research Program, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Kenneth R. Boheler PhD (Investigator) (Investigator)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Weitzer, G. (2006). Embryonic Stem Cell-Derived Embryoid Bodies: An In Vitro Model of Eutherian Pregastrulation Development and Early Gastrulation. In: Wobus, A.M., Boheler, K.R. (eds) Stem Cells. Handbook of Experimental Pharmacology, vol 174. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31265-X_2

Download citation

Publish with us

Policies and ethics

Search

Navigation