Skip to main content
SpringerLink
Log in

Embryonic Stem Cells

Isolation and Application of Pluripotent Cells from Pregastrulation Mammalian Embryo

  • Chapter
Stem Cells Handbook

  • 371 Accesses

Abstract

Pluripotent embryonic stem (ES) cells have been isolated from both mouse and human blastocysts. In vitro, these cells can be differentiated to a diverse range of functional progenitor and terminally differentiated cells. Characterization of this capability has led to recognition of the roles of growth factors and cell-cell and cell-extracellular matrix interactions in the determination of cell fate. The development of increasingly more sophisticated differentiation protocols for the formation of mature cell types will extend the utility of ES cells to allow the production of cell populations, such as those enriched in hematopoietic cells, cardiomyocytes, and neuronal cells, for use in cell replacement therapies for human disease.

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 199.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 259.00
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

  • Abdel-Rahman, B., Fiddler, M., Rappolee, D., and Pergament, E. (1995) Expression of transcription regulating genes in human preimplantation embryos. Hum. Reprod. 10:2787–2792.

    PubMed  CAS  Google Scholar 

  • Adelman, C. A., Chattopadhyay, S., and Bieker, J. (2002) The BMP/ BMPR/Smad pathway directs expression of the erythroid-specific EKLF and GATA1 transcription factors during embryoid body differentiation in serum-free medium. Development 129:539–549.

    PubMed  CAS  Google Scholar 

  • Amit, M., Carpenter, M. K., Inokuma, M. S., et al. (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol. 227:271–278.

    Article  PubMed  CAS  Google Scholar 

  • Armstrong, L., Lako, M., Lincoln, J., Cairns, P. M., and Hole, N. (2000) mTert expression correlates with telomerase activity during the differentiation of murine embyronic stem cells. Mech. Dev. 97: 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Arnhold, S., Lenartz, D., Kruttwig, K., et al. (2000) Differentiation of green fluorescent protein-labelled embryonic stem cell-derived neural precursor cells into Thy-1-positive neurons and glia after transplantation into adult rat striatum. J. Neurosurg. 93:1026–1032.

    Article  PubMed  CAS  Google Scholar 

  • Bagutti, C., Hutter, C., Chiquet-Ehrismann, R., Fassler, R., and Watt, F. M. (2001) Dermal fibroblast-derived growth factors restore the ability of β1; integrin-deficient embryonal stem cells to differentiate into keratinocytes. Dev. Biol 231:321–333.

    Article  PubMed  CAS  Google Scholar 

  • Bain, G., Kitchens, D., Yao, M., Huettner, J. E., and Gottlieb, D. I. (1996) Embryonic stem cells express neuronal properties in vitro. Dev. Biol. 168:342–357.

    Article  Google Scholar 

  • Barbacci, E., Reber, M., Ott, M., Breillat, C., Huetz, F., and Cereghini, S. (1999) Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification. Development 126:4795–4805.

    PubMed  CAS  Google Scholar 

  • Beddington, R. S. P. and Robertson, E. J. (1989) An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 105:733–737.

    PubMed  CAS  Google Scholar 

  • Ben-Shushan, E., Thompson, J. R., Gudas, L. J., and Bergman, Y. (1998) Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site. Mol. Cell. Biol. 18:1866–1878.

    PubMed  CAS  Google Scholar 

  • Beppu, H., Kawabata, M., Hamamoto, T., et al. (2000) BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev. Biol. 221:249–258.

    Article  PubMed  CAS  Google Scholar 

  • Bettess, M. D. (2001) Purification, identification and characterisation of signals directing embryonic stem (ES) cell differentiation. In: Department of Molecular Biosciences Adelaide University, Adelaide, South Australia.

    Google Scholar 

  • Björklund, L. M., Sanchez-Pernaute, R., Chung, S., et al. (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl. Acad. Sci. USA 99:2344–2349.

    Article  PubMed  CAS  Google Scholar 

  • Brook, F. A. and Gardner, R. L. (1997) The origin and efficient derivation of embryonic stem cells in the mouse. Proc. Natl. Acad. Sci. USA 94: 5709–5712.

    Article  PubMed  CAS  Google Scholar 

  • Brüstle, O., Spiro, A. C., Karram, K., Choudray, K., Okabe, S. and McKay, R. D. G. (1997) In vitro-generated neural precursors participate in mammalian brain development. Proc. Natl. Acad. Sci. USA 94: 14,809–14,814.

    Google Scholar 

  • Brüstle, O., Jones, K. N., Learish, R. D., et al. (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285:754–756.

    Article  PubMed  Google Scholar 

  • Burdon, T., Stracey, C., Chambers, I., Nichols, J., and Smith, A. (1999) Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells. Dev. Biol. 210:30–43.

    Article  PubMed  CAS  Google Scholar 

  • Carpenter, M. K, Inokuma, M. S., Denham, J., Mujtaba, T., Chiu, C. P., and Rao, M. S. (2001) Enrichment of neurons and neural precursors from human embryonic stem cells. Exp. Neurol. 172:383–397.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J. C., and Keller, G. (1998) A common precursor for hematopoietic and endothelial cells. Development 125:725–732

    PubMed  CAS  Google Scholar 

  • Ciruna, B. G., Schwartz, L., Harpal K., Yamaguchi, T. P., and Rossant, J. (1997) Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. Development 124:2829–2841.

    PubMed  CAS  Google Scholar 

  • Conovar, J. C., Ip, N. Y., Poueymirou, W. T., et al. (1993) Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells. Development 119:559–565.

    Google Scholar 

  • Coucouvanis, E. and Martin, G. R. (1995) Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo. Cell 83:279–287.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Dani, C., Chambers, I., Johnstone, S., et al. (1998) Paracrine induction of stem cell renewal by LIF-deficient cells: a new ES cell regulatory pathway. Dev. Biol. 203:149–162.

    Article  PubMed  CAS  Google Scholar 

  • Doetschman, T. C., Eistetter, H., Katz, M., Schmidt, W., and 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.

    PubMed  CAS  Google Scholar 

  • Doevendans, P. A., Kubalak, S. W., An, R. H., Becker, D. K., Chien, K. R., and Kass, R. S. (2000) Differentiation of cardiomyocytes in floating embryoid bodies is comparable to fetal cardiomyocytes. J. Mol. Cell Cardiol 32:839–851.

    Article  PubMed  CAS  Google Scholar 

  • Eiges, R., Schuldiner, M., Drukker, M., Yanuka, O., Itskovitz-Eldor, J., and Benvenisty, N. (2001) Establishment of human embryonic stem cell-transfected clones carrying a marker for undifferentiated cells. Curr.Biol. 11:514–518.

    Article  PubMed  CAS  Google Scholar 

  • Ernst, M., Novak, U., Nicholson, S. E., Layton, J. E., and Dunn, A. R. (1999) The carboxyl-terminal domains of gpl30-related cytokine receptors are necessary for suppressing embryonic stem cell differentiation. J. Biol. Chem. 274:9729–9737.

    Article  PubMed  CAS  Google Scholar 

  • Evans, M. J. and Kaufman, M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156.

    Article  PubMed  CAS  Google Scholar 

  • Fairchild, P. J., Brook, F. A., Gardner, R. L., et al. (2000) Directed differentiation of dendritic cells from mouse embryonic stem cells. Curr. Biol 10:1515–1518.

    Article  PubMed  CAS  Google Scholar 

  • Faloon, P., Arentson, E., Kazarov, A., et al. (2000) Basic fibroblast growth factor positively regulates hematopoietic development. Development 127:1931–1941.

    PubMed  CAS  Google Scholar 

  • Ferrara, N., Carver-Moore, K., Chen, H., et al. (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442.

    Article  PubMed  CAS  Google Scholar 

  • Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., and Samarut, J. (1995) In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J. Cell Sci. 108:3181–3188.

    PubMed  CAS  Google Scholar 

  • Gearing, D. P. and Bruce, G. (1992) Oncastatin M binds the high-affinity leukemia inhibitory factor receptor. New Biol. 4:61–65.

    PubMed  CAS  Google Scholar 

  • Guan, K., Chang, H., Rolletschek, A., and Wobus, A. M. (2001) Embryonic stem cell-derived neurogenesis. Retinoic acid induction and lineage selection of neuronal cells. Cell Tissue Res. 305:71–76.

    Article  CAS  Google Scholar 

  • Hahnel, A. C., Rappolee, D. A., Millan, J. L., et al. (1990) Two alkaline phosphatase genes are expressed during early development in the mouse embryo. Development 10:555–564.

    Google Scholar 

  • Handyside, A. H., O’Neill, G. T., Jones, M., and Hooper, M. L. (1989) Use of BRL-conditioned medium in combination with feeder layers to isolate a diploid embryonal stem cell line. Roux’s Arch. Dev. Biol 198:48–55.

    Article  Google Scholar 

  • Heath, J. K., Paterno, G. D., Lindon, A. C., and Edwards, D. R. (1989) Expression of multiple heparin-binding growth factor species by murine embryonal carcinoma and embryonic stem cells. Development 107:113–122.

    PubMed  CAS  Google Scholar 

  • Hébert, J. M., Boyle, M., and Martin, G. M. (1991) mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation. Development 112:407–415.

    PubMed  Google Scholar 

  • Hogan, B. L. and Tilly, R. (1981) Cell interactions and endoderm differentiation in cultured mouse embryos. J. Embryol Exp. Morphol. 62:79–394.

    Google Scholar 

  • Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., et al. (2000) Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol. Med. 6:88–95.

    PubMed  CAS  Google Scholar 

  • Johansson, B. M and Wiles, M. V. (1995) Evidence for involvement of activin a and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol. Cell Biol. 15:141–151.

    PubMed  CAS  Google Scholar 

  • Kaufman, D. S., Hanson, E. T., Lewis, R. L., Auerbach, R., and Thomson, J. A. (2001) Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 98:10,716–10,721.

    Article  Google Scholar 

  • Kawasaki, H., Mizuseki, K., Nishikawa, S., et al. (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40.

    Article  PubMed  CAS  Google Scholar 

  • Kehat, I., Kenyagin-Karsenti, D., Snir, M., et al. (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest. 108:407–414.

    PubMed  CAS  Google Scholar 

  • Kennedy, M., Firpo, M., Choi, K., et al. (1997) A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386: 488–493.

    Article  PubMed  CAS  Google Scholar 

  • Klug, M. G., Soonpaa, M. H., Koh, G. Y., and Field, L. J. (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98:216–224.

    Article  PubMed  CAS  Google Scholar 

  • Kolossov, E., Fleischmann, B. K., Liu, Q., et al. (1998) Functional characteristics of ES cell-derived cardiac precursor cells identified by tissue-specific expression of the green fluorescent protein. J. Cell Biol. 143:2045–2056.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lee, S. H., Lumelsky, N., Studer, L., Auerbach, J. M., and McKay, R. D. (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat. Biotechnol. 18:675–679.

    Article  PubMed  CAS  Google Scholar 

  • Li, M., Sendtner, M., and Smith, A. (1995) Essential function of LIF receptor in motor neurons. Nature 378:724–727.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Chen, Y., Scheele, S., et al. (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  PubMed  CAS  Google Scholar 

  • Liu, S., Qu, Y., Stewart, T. J., et al. (2000) Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc. Natl. Acad. Sci. USA 97:6126–6131.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Matsuda, T., Nakamura, T., Nakao, K., et al. (1999) STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J. 18:4261–4269.

    Article  PubMed  CAS  Google Scholar 

  • McDonald, J. W., Liu, X.-Z., Qu, Y., et al. (1999) Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat. Med. 5:1410–1412.

    Article  PubMed  CAS  Google Scholar 

  • McWhir, J., Schnieke, A. E., Ansell, R., et al. (1996) Selective ablation of differentiated cells permits isolation of embryonic stem cell lines from murine embryos with a non-permissive genetic background. Nat. Genet. 14:223–226.

    Article  PubMed  CAS  Google Scholar 

  • Meehan, R. R., Barlow, D. P., Hill, R. E., Hogan, B. L. M., and Hastie, R. E. (1984) Pattern of serum protein gene expression in mouse visceral yolk sac and foetal liver. EMBO J. 3:1881–1885.

    PubMed  CAS  Google Scholar 

  • Miquerol, L., Gertsenstein, M., Harpal, K., Rossant, J., and Nagy, A. (1999) Multiple developmental roles of VEGF suggested by a LacZ-tagged allele. Dev. Biol 212:307–322.

    Article  PubMed  CAS  Google Scholar 

  • Mishina, Y., Suzuki, A., Ueno, N., and Behringer, R. R. (1995) Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev.9: 3027–3037

    Article  PubMed  CAS  Google Scholar 

  • Mountford, P., Nichols, J., Zevnik, B., O’ Brien, C., and Smith, A. (1998) Maintenance of pluripotential embryonic stem cells by stem cell selection. Reprod. Fertil. Dev. 10:527–533.

    Article  PubMed  CAS  Google Scholar 

  • Muller, M., Fleischmann, B. K., Seibert, S., et al. (2000) Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J. 14: 2540–2548.

    Article  CAS  Google Scholar 

  • Murray, P. and Edgar, D. (2000) Regulation of programmed cell death by basement membranes in embryonic development. J. Cell Biol. 150: 1215–1221.

    Article  PubMed  CAS  Google Scholar 

  • Nakano, T., Kodama, H., and Honjo, T. (1994) Generation of lympho-hematopoietic cells from embryonic stem cells in culture. Science 265: 1098–1101.

    Article  PubMed  CAS  Google Scholar 

  • Nakayama, N., Lee, J., and Chiu, L. (2000) Vascular endothelial growth factor synergistically enhances bone morphogenetic proteins-dependent lymphohematopoietic cell generation from embryonic stem cells in vitro. Blood 95:2275–2283.

    PubMed  CAS  Google Scholar 

  • Nichols, J., Evans, E. P., and Smith, A. G. (1990) Establishment of germ-line-competent embryonic stem (ES) cells using differentiation inhibiting activity. Development 110:1341–1348.

    PubMed  CAS  Google Scholar 

  • Nichols, J., Chambers, I., and Smith, A. (1994) Derivation of germline competent embryonic stem cells with a combination of interleukin-6 and soluble interleukin-6 receptor. Exp. Cell Res. 215:237–239.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, J., Davidson, D., Taga, T., Yoshida, K., Chambers, I., and Smith, A. (1996) Complementary tissue-specific expression of LIF and LIF-receptor mRNAs in early mouse embryogenesis. Mech. Dev. 57:123–131.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, J., Zevnik, B., Anastassiadis, K., et al. (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391

    Article  PubMed  CAS  Google Scholar 

  • Nichols, J., Chambers, I., Taga, T., and Smith, A. (2001) Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines. Development 128:2333–2339.

    PubMed  CAS  Google Scholar 

  • Nishikawa, S. I., Nishikawa, S., Hirashima, M., Matsuyoshi, N., and Kodama, H. (1998) Progressive lineage analysis by cell sorting and culture identifies FLK1+ VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. Development 125:1747–1757.

    PubMed  CAS  Google Scholar 

  • Niswander, L. and Martin, G. R. (1992) Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. Development 114:755–768.

    PubMed  CAS  Google Scholar 

  • Niwa, H. (2001) Molecular mechanisms to maintain stem cell renewal of ES cells. Cell Struct. Fund. 26:137–148.

    Article  CAS  Google Scholar 

  • Niwa, H., Burdon, T., Chambers, I., and Smith, A. (1998) Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12:2048–2060.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Okabe, S., Forsberg-Nilsson, K., Spiro, A. C., Segal, M., and McKay, R. D. (1996) Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech. Dev. 59:89–102.

    Article  PubMed  CAS  Google Scholar 

  • Pease, S., Braghetta, P., Gearing, D., Grail, D., and Williams, R. L. (1990) Isolation of embryonic stem (ES) cells in media supplemented with recombinant leukemia inhibitory factor (LIF). Dev. Biol. 141: 344–352.

    Article  PubMed  CAS  Google Scholar 

  • Pelton, T. A., Bettess, M. D., Lake, J., Rathjen, J., and Rathjen, P. D. (1998) Developmental complexity of early mammalian pluripotent cell populations in vivo and in vitro. Reprod. Fertil. Dev. 10: 535–549.

    Article  PubMed  CAS  Google Scholar 

  • Pelton, T. A., Sharma, S., Schulz, T. C., Rathjen, J., and Rathjen, P. D. (2002) Transient pluripotent cell populations during primitive ectoderm formation: correlation of in vivo and in vitro pluripotent cell development. J. Cell Sci. 115:329–339.

    PubMed  CAS  Google Scholar 

  • Pennica, D., Shaw, K. J., Swanson, T. A., et al. (1995) Cardiotrophin-1: biological activities and binding to the leukemia inhibitory factor receptor/gpl30 signalling complex. J. Biol. Chem. 270:10,915–10,922.

    Google Scholar 

  • Pera, M. F., Reubinoff, B., and Trounson, A. (2000) Human embryonic stem cells. J. Cell Sci. 113:5–10.

    PubMed  CAS  Google Scholar 

  • Prelle, K., Vassiliev, I. M., Vassilieva, S. G., Wolf, E., and Wobus, A. M. (1999) Establishment of pluripotent cell lines from vertebrate species—present status and future prospects. Cells Tissues Organs 165:220–236.

    Article  PubMed  CAS  Google Scholar 

  • Quinlan, G. A., Williams, E. A., Tan, S.-S., and Tarn, P. L. (1995) Neurectodermal fate of epiblast cells in the distal region of the mouse egg cylinder: implications for body plan orgaization during early embryogenesis. Development 121:87–98.

    PubMed  CAS  Google Scholar 

  • Rathjen, J. and Rathjen, P. D. (2002) Formation of neural cell populations by differentiation of embryonic stem cells in vitro. Sci. World2: 690–700.

    CAS  Google Scholar 

  • Rathjen, J., Lake, J.-A., Bettess, M. D., Washington, J. M., Chapman, G., and Rathjen, P. D. (1999) Formation of a primitive ectoderm like cell population from ES cells in response to biologically derived factors. J. Cell Sci. 112:601–612.

    PubMed  CAS  Google Scholar 

  • Rathjen, J., Dunn, S., Bettess, M. D., and Rathjen, P. D. (2001) Lineage specific differentiation of pluripotent cells in vitro: a role for extraembryonic cell types. Reprod. Fertil. Dev. 13:15–22.

    Article  PubMed  CAS  Google Scholar 

  • Rathjen, J., Haines, B. P., Hudson, K. M., Nesci, A., Dunn, S., and Rathjen, P. D. (2002) Directed differentiation of pluripotent cells to neural lineages: homogeneous formation and differentiation of a neurectoderm population. Development 129:2649–2661.

    PubMed  CAS  Google Scholar 

  • Rathjen, P. D., Nichols, J., Toth, S., Edwards, D. R., Heath, J. K., and Smith, A. G. (1990) Developmentally programmed induction of differentiating inhibiting activity and the control of stem cell populations. Genes Dev. 4:2308–2318.

    Article  PubMed  CAS  Google Scholar 

  • Reubinoff, B. E., Pera, M. F., Fong, C.-Y., Trounson, A., and Bongso, A. (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18:399–404.

    Article  PubMed  CAS  Google Scholar 

  • Reubinoff, B. E., Itsykson, P., Turetsky, T., et al. (2001) Neural progenitors from human embryonic stem cells. Nat. Biotechnol. 19: 1134–1140.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Robertson, S. M., Kennedy, M., Shannon, J. M., and Keller, G. (2000) A transitional stage in the commitment of mesoderm to hematopoie-sis requiring the transcription factor SCL/tal-1. Development 127: 2447–2459.

    PubMed  CAS  Google Scholar 

  • Rodda, S. J., Kavanagh, S. J., Rathjen, J., and Rathjen, P. D. (2002) Embryonic stem cell differentiation and the analysis of mammalian development. Int. J. Dev. Biol. 46:449–458.

    PubMed  CAS  Google Scholar 

  • Rogers, M. B., Hosier, B. A., and Gudas, L. (1991) Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplan-tation embryos, trophoblast and spermatocytes. Development 113: 815–824.

    PubMed  CAS  Google Scholar 

  • Rose, T. M., Weiford, D. M., Gunderson, N. L., and Bruce, A. G. (1994) Oncostatin M (OSM) inhibits the differentiation of pluripotent embryonic stem cells in vitro. Cytokine 6:48–54.

    Article  PubMed  CAS  Google Scholar 

  • Rosner, M. H., Vigano, M. A., Ozato, K., et al. (1990) A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345:686–692.

    Article  PubMed  CAS  Google Scholar 

  • Rossant, J. (1993) Immortal germ cells? Curr. Biol. 3:47–49.

    Article  PubMed  CAS  Google Scholar 

  • Rossant, J. (1995) Development of the extraembryonic lineages. Semin. Dev. Biol. 6:237–247.

    Article  Google Scholar 

  • Schöler, H. R., Dressler, G. R., Balling, R., Rohdewohld, H., and Gruss, P. (1990) Oct-4: a germline-specific transcription factor mapping to the mouse t-complex. EMBO J. 9:2185–2195.

    PubMed  Google Scholar 

  • Schuldiner, M., Yanuka, O., Itskiovitz-Eldor, J., Melton, D. A., and Benvenisty, N. (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 97:11,307–11,312.

    Article  Google Scholar 

  • Schuldiner, M., Eiges, R., Eden, A., et al. (2001) Induced neuronal differentiation of human embryonic stem cells. Brain Res. 913:201–205.

    Article  PubMed  CAS  Google Scholar 

  • Sefton, M., Johnson, M. H., and Clayton, L. (1992) Synthesis and phosphorylation of uvomorulin during mouse early development. Development 115:313–318.

    PubMed  CAS  Google Scholar 

  • Shen, M. M. and Leder, P. (1992) Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro. Proc. Natl. Acad. Sci. USA 89:8240–8244.

    Article  PubMed  CAS  Google Scholar 

  • Smith, A. (1998) Cell therapy: in search of pluripotency. Curr. Biol. 8:R802–R804.

    Article  Google Scholar 

  • Smith, A. G. (1991) Culture and differentiation of embryonic stem cells. J. Tissue Cult. Methods 13:89–94.

    Article  Google Scholar 

  • Smith, A. G. and Hooper, M. L. (1987) Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells. Dev. Biol. 121:1–9.

    Article  PubMed  CAS  Google Scholar 

  • Smith, A., Heath, J. K., Donaldson, D. D., et al. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336:688–690.

    Article  PubMed  CAS  Google Scholar 

  • Solter, D. and Knowles, B. B. (1978) Monoclonal antibody defining stage-specific mouse embryonic antigen (SSEA-1). Proc. Natl. Acad. Sci. USA 75:5565–5569.

    Article  PubMed  CAS  Google Scholar 

  • Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A., and Martin, F. (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49:157–162.

    Article  PubMed  CAS  Google Scholar 

  • Strübing, C., Ahnert-Hilger, G., Shan J., Wiedenmann, B., Hescheler, J., and Wobus, A. M. (1995) Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech. Dev. 53:275–287.

    Article  PubMed  Google Scholar 

  • Thomas, K. R. and Capecchi, M. R. (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–512.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  • Tropepe, V., Hitoshi, S., Sirard, C., Mak, T. W., Rossant, J., and van der Kooy, D. (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30:65–78.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, M., Wedemeyer, J., Ganiatsas, S., Tarn, S. Y., Zon, L. I., and Galli, S. J. (2000) In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo. Proc. Natl. Acad. Sci. USA 97:9186–9190.

    Article  PubMed  CAS  Google Scholar 

  • van Eijk, M. J., van Rooijen, M. A., Modina, S., et al. (1999) Molecular cloning, genetic mapping, and developmental expression of bovine POU5F1. Biol. Reprod. 60:1093–1103.

    Article  PubMed  Google Scholar 

  • Ware, C. B., Horowitz, M. C., Renshaw, B. R., et al. (1995) Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 121:1283–1299.

    PubMed  CAS  Google Scholar 

  • Wiles, M. V. and Johansson, B. M. (1999) Embryonic stem cell development in a chemically defined medium. Exp. Cell Res. 247: 241–248.

    Article  PubMed  CAS  Google Scholar 

  • Williams, P. L., Hilton, D. J., Pease, S., et al. (1988) Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336:684–687.

    Article  PubMed  CAS  Google Scholar 

  • Winnier, G., Blessing, M., Labosky, P. A., and Hogan, B. L. M. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9:2105–2116.

    Article  PubMed  CAS  Google Scholar 

  • Xu, C., Inokuma, M. S., Denham, J., et al. (2001) Feeder-free growth of undifferentiated human embryonic stem cells. Nat. Biotechnol. 19: 971–974.

    Article  PubMed  CAS  Google Scholar 

  • Yamashita, J., Itoh, H., Hirashima, M., et al. (2000) Flkl-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408:92–93.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida, K., Chambers, I., Nichols, J., et al. (1994) Maintenance of the pluripotent phenotype of embryonic stem cells through direct activation of gpl30 signalling pathways. Mech. Dev. 45:163–171.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida, K., Taga, T., Saito, M., et al. (1996) Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc. Natl. Acad. Sci. USA 93:407–411.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, S.C., Wernig, M., Duncan, I. D., Brustle, O., and Thomson, J. A. (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat. Biotechnol. 19: 1129–1133.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Joy Rathjen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter David Rathjen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wadsworth Center and Ordway Research Institute, Empire State Plaza, Albany, NY, USA

    Stewart Sell MD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rathjen, J., Rathjen, P.D. (2004). Embryonic Stem Cells. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-411-5_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-367-1

  • Online ISBN: 978-1-59259-411-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation