XEN and the Art of Stem Cell Maintenance: Molecular Mechanisms Maintaining Cell Fate and Self-Renewal in Extraembryonic Endoderm Stem (XEN) Cell Lines

Chapter
Part of the Advances in Anatomy, Embryology and Cell Biology book series (ADVSANAT, volume 229)

Abstract

The extraembryonic endoderm is one of the first cell types specified during mammalian development. This extraembryonic lineage is known to play multiple important roles throughout mammalian development, including guiding axial patterning and inducing formation of the first blood cells during embryogenesis. Moreover, recent studies have uncovered striking conservation between mouse and human embryos during the stages when extraembryonic endoderm cells are first specified, in terms of both gene expression and morphology. Therefore, mouse embryos serve as an excellent model for understanding the pathways that maintain extraembryonic endoderm cell fate. In addition, self-renewing multipotent stem cell lines, called XEN cells, have been derived from the extraembryonic endoderm of mouse embryos. Mouse XEN cell lines provide an additional tool for understanding the basic mechanisms that contribute to maintaining lineage potential, a resource for identifying how extraembryonic ectoderm specifies fetal cell types, and serve as a paradigm for efforts to establish human equivalents. Given the potential conservation of essential extraembryonic endoderm roles, human XEN cells would provide a considerable advance. However, XEN cell lines have not yet been successfully derived from human embryos. Given the potential utility of human XEN cell lines, this chapter focuses on reviewing the mechanisms known to govern the stem cell properties of mouse XEN, in hopes of facilitating new ways to establish human XEN cell lines.

Notes

Acknowledgements

This work is supported by NIH R01 GM104009.

References

  1. Artus J, Panthier JJ, Hadjantonakis AK (2010) A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst. Development 137:3361–3372CrossRefPubMedPubMedCentralGoogle Scholar
  2. Artus J, Douvaras P, Piliszek A, Isern J, Baron MH, Hadjantonakis AK (2012) BMP4 signaling directs primitive endoderm-derived XEN cells to an extraembryonic visceral endoderm identity. Dev Biol 361:245–262CrossRefPubMedGoogle Scholar
  3. Belaoussoff M, Farrington SM, Baron MH (1998) Hematopoietic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo. Development 125:5009–5018PubMedGoogle Scholar
  4. Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S, Howlett S, Clarkson A, Ahrlund-Richter L, Pedersen R, Vallier L (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191–195CrossRefPubMedGoogle Scholar
  5. Cho LT, Wamaitha SE, Tsai IJ, Artus J, Sherwood RI, Pedersen RA, Hadjantonakis AK, Niakan KK (2012) Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states. Development 139:2866–2877CrossRefPubMedPubMedCentralGoogle Scholar
  6. de Sousa Lopes SM, Roelen BA, Monteiro RM, Emmens R, Lin HY, Li E, Lawson KA, Mummery CL (2004) BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev 18:1838–1849CrossRefPubMedPubMedCentralGoogle Scholar
  7. Deglincerti A, Croft GF, Pietila LN, Zernicka-Goetz M, Siggia ED, Brivanlou AH (2016) Self-organization of the in vitro attached human embryo. Nature 533:251–254CrossRefPubMedGoogle Scholar
  8. Evans M, Kaufman M (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156CrossRefPubMedGoogle Scholar
  9. Gardner R (1982) Investigation of cell lineage and differentiation in the extraembryonic endoderm of the mouse embryo. J Embryol Exp Morphol 68:175–198PubMedGoogle Scholar
  10. Kang M, Piliszek A, Artus J, Hadjantonakis AK (2013) FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse. Development 140:267–279CrossRefPubMedPubMedCentralGoogle Scholar
  11. Kuijk EW, van Tol LT, Van de Velde H, Wubbolts R, Welling M, Geijsen N, Roelen BA (2012) The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos. Development 139:871–882CrossRefPubMedPubMedCentralGoogle Scholar
  12. Kunath T, Arnaud D, Uy GD, Okamoto I, Chureau C, Yamanaka Y, Heard E, Gardner RL, Avner P, Rossant J (2005) Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts. Development 132:1649–1661CrossRefPubMedGoogle Scholar
  13. Lin J, Khan M, Zapiec B, Mombaerts P (2016) Efficient derivation of extraembryonic endoderm stem cell lines from mouse postimplantation embryos. Sci Rep 6:39457CrossRefPubMedPubMedCentralGoogle Scholar
  14. Madabhushi M, Lacy E (2011) Anterior visceral endoderm directs ventral morphogenesis and placement of head and heart via BMP2 expression. Dev Cell 21:907–919CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mao J, McKean DM, Warrier S, Corbin JG, Niswander L, Zohn IE (2010) The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure. Development 137:3079–3088CrossRefPubMedPubMedCentralGoogle Scholar
  16. Martin G (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638CrossRefPubMedPubMedCentralGoogle Scholar
  17. McDonald AC, Biechele S, Rossant J, Stanford WL (2014) Sox17-mediated XEN cell conversion identifies dynamic networks controlling cell-fate decisions in embryo-derived stem cells. Cell Rep 9:780–793CrossRefPubMedGoogle Scholar
  18. Niakan KK, Schrode N, Cho LT, Hadjantonakis AK (2013) Derivation of extraembryonic endoderm stem (XEN) cells from mouse embryos and embryonic stem cells. Nat Protoc 8:1028–1041CrossRefPubMedPubMedCentralGoogle Scholar
  19. Nichols J, Silva J, Roode M, Smith A (2009) Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136:3215–3222CrossRefPubMedPubMedCentralGoogle Scholar
  20. Paca A, Séguin CA, Clements M, Ryczko M, Rossant J, Rodriguez TA, Kunath T (2012) BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm. Dev Biol 361:90–102CrossRefPubMedGoogle Scholar
  21. Parenti A, Halbisen M, Wang K, Latham K, Ralston A (2016) OSKM induce extraembryonic endoderm stem cells in parallel to iPS cells. Stem Cell Reports 6(4):447–455Google Scholar
  22. Roode M, Blair K, Snell P, Elder K, Marchant S, Smith A, Nichols J (2012) Human hypoblast formation is not dependent on FGF signalling. Dev Biol 361:358–363CrossRefPubMedPubMedCentralGoogle Scholar
  23. Rossant J (2015) Mouse and human blastocyst-derived stem cells: vive les differences. Development 142:9–12CrossRefPubMedGoogle Scholar
  24. Rugg-Gunn PJ, Cox BJ, Ralston A, Rossant J (2010) Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo. Proc Natl Acad Sci USA 107:10783–10790CrossRefPubMedPubMedCentralGoogle Scholar
  25. Séguin CA, Draper JS, Nagy A, Rossant J (2008) Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells. Cell Stem Cell 3:182–195CrossRefPubMedGoogle Scholar
  26. Senner CE, Krueger F, Oxley D, Andrews S, Hemberger M (2012) DNA methylation profiles define stem cell identity and reveal a tight embryonic-extraembryonic lineage boundary. Stem Cells 30:2732–2745CrossRefPubMedGoogle Scholar
  27. Shahbazi MN, Jedrusik A, Vuoristo S, Recher G, Hupalowska A, Bolton V, Fogarty NM, Campbell A, Devito LG, Ilic D, Khalaf Y, Niakan KK, Fishel S, Zernicka-Goetz M (2016) Self-organization of the human embryo in the absence of maternal tissues. Nat Cell Biol 18:700–708CrossRefPubMedPubMedCentralGoogle Scholar
  28. Shimosato D, Shiki M, Niwa H (2007) Extra-embryonic endoderm cells derived from ES cells induced by GATA factors acquire the character of XEN cells. BMC Dev Biol 7:80CrossRefPubMedPubMedCentralGoogle Scholar
  29. Spruce T, Pernaute B, Di-Gregorio A, Cobb BS, Merkenschlager M, Manzanares M, Rodriguez TA (2010) An early developmental role for miRNAs in the maintenance of extraembryonic stem cells in the mouse embryo. Dev Cell 19:207–219CrossRefPubMedGoogle Scholar
  30. Tanaka S, Kunath T, Hadjantonakis AK, Nagy A, Rossant J (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282:2072–2075CrossRefPubMedGoogle Scholar
  31. Tesar P, Chenoweth J, Brook F, Davies T, Evans E, Mack D, Gardner R, McKay R (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:196–199CrossRefPubMedGoogle Scholar
  32. Thomas P, Beddington R (1996) Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr Biol 6:1487–1496CrossRefPubMedGoogle Scholar
  33. Verzi MP, Shin H, He HH, Sulahian R, Meyer CA, Montgomery RK, Fleet JC, Brown M, Liu XS, Shivdasani RA (2010) Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell 19:713–726CrossRefPubMedPubMedCentralGoogle Scholar
  34. Wamaitha SE, del Valle I, Cho LT, Wei Y, Fogarty NM, Blakeley P, Sherwood RI, Ji H, Niakan KK (2015) Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells. Genes Dev 29:1239–1255CrossRefPubMedPubMedCentralGoogle Scholar
  35. Yamanaka Y, Lanner F, Rossant J (2010) FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137:715–724CrossRefPubMedGoogle Scholar
  36. Zhao Y, Zhao T, Guan J, Zhang X, Fu Y, Ye J, Zhu J, Meng G, Ge J, Yang S, Cheng L, Du Y, Zhao C, Wang T, Su L, Yang W, Deng H (2015) A XEN-like state bridges somatic cells to pluripotency during chemical reprogramming. Cell 163:1678–1691CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyMichigan State UniversityEast LansingUSA
  2. 2.Reproductive and Developmental Sciences ProgramMichigan State UniversityEast LansingUSA

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