Skip to main content

Stem Cells from Early Mammalian Embryos

Common Themes and Significant Differences

  • Chapter
Stem Cells Handbook

Abstract

A description of the potential of cells during embryonic development indicates that the first restriction of the totipoten-tiality in the zygote occurs during formation of the blastocyst when the outer layer of cells forms the trophectoderm, which will give rise to the placenta, and the inner cells form the inner cell mass (ICM), which will develop into the fetus and fetal membranes. At this point, the ICM cells lose the ability to form trophectoderm and are considered pluripotent in that they can form all the cells of the body of the embryo, but not the placenta. A population of pluripotent cells persists for several days, but later in development, pluripotency is limited to the primordial germ cells (PGCs), which will eventually give rise to the gametes. A variety of methods have been devised to harness the stem cell capacity of early embryo-derived cells in vitro. Historically, mouse teratocarcinoma stem cells and embryonal carcinoma stem cells were the first to be derived. They were isolated from spontaneously occurring germ cell tumors or from tumors derived from embryo ectopic expiants, respectively. They can be propagated indefinitely in vitro and have the capacity to differentiate into many cell types. More recently, three stem cell types have been isolated directly from the early embryo, without the intervening tumor growth: embryonic stem (ES) cells from the ICM of the blastocyst, trophectoderm stem (TS) cells from the trophectoderm of the blastocyst or the extraembryonic ectoderm, and embryonic germ (EG) cells from the PGCs. ES cells and EG cells are similar in their pluripotency and capacity for indefinite self-renewal, whereas TS cells have a more restricted developmental potential. No truly totipotent stem cell line has yet been derived, but the phenotype of ES lines can be changed to TS under appropriate culture conditions, indicating that transdifferentiation is possible. Recently, ES and EG cell lines, which share many but not all of the characteristics of mouse stem cell lines, have been derived from human embryos.

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

Access this chapter

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

  • Arman, E., Haffner-Krausz, R., Chen, Y., Heath, J. K., and Lonai, P. (1998) Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc. Natl. Acad. Sci. USA 95:5082–5087.

    Article  PubMed  CAS  Google Scholar 

  • Axelrod, H. R. (1984) Embryonic stem cell lines derived from blastocysts by a simplified technique. Dev. Biol. 101:225–228.

    Article  PubMed  CAS  Google Scholar 

  • Beddington, R. S. 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 

  • Brazelton, T. R., Rossi, F. M. V., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: Expression of neuronal phenotypes in adult mice. Science 290:1775–1779.

    Article  PubMed  CAS  Google Scholar 

  • Brinster, R. L. (1974) The effect of cells transferred into the mouse blastocyst on subsequent development. J. Exp. Med. 140:1049–1056.

    Article  PubMed  CAS  Google Scholar 

  • Brivanlou, A. H., Gage, F. H., Jaenisch, R., Jessell, T., Melton, D., Rossant, J. (2003) Setting standards for human embryonic stem cells. Science 300:913–916.

    Article  PubMed  CAS  Google Scholar 

  • Chai, N., Patel, Y., Jacobson, K., McMahon, J., McMahon, A., and Rappolee, D. (1998) FGF is an essential regulator of the fifth cell division in preimplantation mouse embryos. Dev. Biol. 198:105–115.

    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 

  • Feldman, B., Poueymirou, W., Papaioannou, V. E., DeChiara, T., and Goldfarb, M. (1995) Requirement of FGF-4 for postimplantation mouse development. Science 267:246–249.

    Article  PubMed  CAS  Google Scholar 

  • Gardner, R. L., Papaioannou, V. E., and Barton, S. C. (1973) Origin of the ectoplacental cone and secondary giant cells in mouse blastocysts reconstituted from isolated trophoblast and inner cell mass. J. Embryol. Exp. Morphol. 30:561–572.

    PubMed  CAS  Google Scholar 

  • Grusby, M. J., Auchincloss, H., Jr., Lee, R., et al. (1993) Mice lacking major histocompatibility complex class I and class II molecules. Proc. Natl. Acad. Sci. USA 90:3913–3917.

    Article  PubMed  CAS  Google Scholar 

  • Hadjantonakis, A.-K. and Papaioannou, V. E. (2001) The stem cells of early mouse embryos. Differentiation 68:159–166.

    Article  PubMed  CAS  Google Scholar 

  • Hadjantonakis, A.-K. and Papaioannou, V. E. (2002) Can mammalian cloning combined with embryonic stem cell technologies be used to treat human diseases? Genome Biol. 3:1023.1–1023.6.

    Article  Google Scholar 

  • Holden, C. (2003) Cells find destiny though merger. Science 300:35.

    Article  PubMed  CAS  Google Scholar 

  • Howell, C. Y., Bestor, T. H., Ding, F., et al. (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104: 829–838.

    Article  PubMed  CAS  Google Scholar 

  • Kunath, T., Strumpf, D., Rossant, J., and Tanaka, S. (2001) Trophoblast stem cells. In: Stem Cell Biology (Marshak, D. R., et al. eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 267–287.

    Google Scholar 

  • Labosky, P. A., Barlow, D. P., and Hogan, B. L. (1994) Mouse embryonic germ (EG) cell lines: transmission through the germline and differences in the methylation imprint of insulin-like growth factor 2 receptor (Igf2r) gene compared with embryonic stem (ES) cell lines. Development 120:3197–3204.

    PubMed  CAS  Google Scholar 

  • Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., and McKay, R. (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394.

    Article  PubMed  CAS  Google Scholar 

  • 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 78:7634–7638.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Medvinsky, A. and Smith, A. (2003) Stem cells: Fusion brings down barriers. Nature 422:823–825.

    Article  PubMed  CAS  Google Scholar 

  • Mintz, B. and Illmensee, K. (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl. Acad. Sci. USA 72:3585–3589.

    Article  PubMed  CAS  Google Scholar 

  • Morrison-Graham, K. and Takahashi, Y. (1993) Steel factor and c-Kit receptor: from mutants to a growth factor system. BioEssays 15: 77–83.

    CAS  Google Scholar 

  • Munsie, M. J., Michalska, A. E., O’Brien, C. M., Trounson, A. O., Pera, M. F., and Mountford, P. S. (2000) Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr. Biol. 10:989–992.

    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 

  • 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 

  • 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 

  • Odorico, J. S., Kaufman, D. S., and Thomson, J. A. (2001) Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19: 193–204.

    Article  PubMed  CAS  Google Scholar 

  • Ohtaka, T., Matsui, Y., and Obinata, M. (1999) Hematopoietic develoment of primordial germ cell-derived mouse embryonic germ cells in culture. Biochem. Biophys. Res. Commun. 260:475–482.

    Article  PubMed  CAS  Google Scholar 

  • Papaioannou, V. E. and Rossant, J. (1983a) Appendix Table 3, EC-embryo chimeras. In: Teratocarcinoma Stem Cells (Silver, L. M., et al. eds.), vol. 10, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 734–735.

    Google Scholar 

  • Papaioannou, V. E. and Rossant, J. (1983b) Effects of the embryonic environment on proliferation and differentiation of embryonal carcinoma cells. Cancer Surv. 2:165–183.

    Google Scholar 

  • Papaioannou, V. E., McBurney, M. W., Gardner, R. L., and Evans, M. J. (1975) Fate of teratocarcinoma cells injected into early mouse embryos. Nature 258:70–73.

    Article  PubMed  CAS  Google Scholar 

  • Papaioannou, V. E., Rossant, J., and Gardner, R. L. (1978) Stem cells in early mammalian development. In: Stem Cells and Tissue Homeostasis. British Society for Cell Biology Symposium2 (Lord, B. I., et al., eds.), Cambridge University Press, Cambridge, MA, pp. 49–69.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rideout, W. M. III, Hochedlinger, K., Kyba, M., Daley, G. Q., and Jaenisch, R. (2002) Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 109:17–27.

    Article  PubMed  CAS  Google Scholar 

  • Robertson, E. J. (1991) Using embryonic stem cells to introduce mutations into the mouse germ line. Biol. Reprod. 44:238–245.

    Article  PubMed  CAS  Google Scholar 

  • Rohwedel, J., Sehlmeyer, U., Shan, J., Meister, A., and Wobus, A. M. (1996) Primordial germ cell-derived mouse embryonic germ EG cells in vitro resemble undifferentiated stem cells with respect to differenciation capacity and cell cycle distribution. Cell Biol. Int. 20: 579–587.

    Article  PubMed  CAS  Google Scholar 

  • Rossant, J. and Ofer, L. (1977) Properties of extra-embryonic ectoderm isolated from postimplantation mouse embryos. J. Embryol. Exp. Morphol. 39:183–194.

    PubMed  CAS  Google Scholar 

  • Rossant, J. and Tamura-Lis, W. (1981) Effect of culture conditions on diploid to giant-cell transformation in postimplantation mouse trophoblast. J. Embryol. Exp. Morphol. 62:217–227.

    PubMed  CAS  Google Scholar 

  • Shamblott, M. J., Axelman, J., Wang, S., et al. (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl Acad. Sci. USA 95:13,726–13,731.

    Article  Google Scholar 

  • Smith, A. (2001) Embryonic stem cells. In: Stem cell Biology (Marshak, D. R., et al., eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 205–230.

    Google Scholar 

  • Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., and Rogers, D. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336:688–690.

    Article  PubMed  CAS  Google Scholar 

  • Solter, D., Skreb, N., and Damjanov, I. (1970) Extrauterine growth of mouse egg-cylinders results in malignant teratoma. Nat. Lond. 227: 503, 504.

    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 49:1–6.

    Article  Google Scholar 

  • Stevens, L. C. (1970) The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev. Biol. 21:364–382.

    Article  PubMed  CAS  Google Scholar 

  • Stevens, L. C. (1983) The origin and development of testicular, ovarian and embryo-derived teratomas. In: Teratocarcinoma Stem Cells, vol. 10, (Silver, L. M., et al., eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 23–36.

    Google Scholar 

  • Stewart, C. L., Gadi, I., and Bhatt, H. (1994) Stem cells from primordial germ cells can reenter the germ line. Dev. Biol. 161:626–628.

    Article  PubMed  CAS  Google Scholar 

  • Surani, M. A. (1998) Imprinting and the initiation of gene silencing in the germ line. Cell 93:309–312.

    Article  PubMed  CAS  Google Scholar 

  • Tada, T., Tada, M., Hilton, K., et al. (1998) Epigenotype switching of imprintable loci in embryonic germ cells. Dev. Genes Evol. 207:551–561.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Terada, N., Hamazaki, T., Oka, M., et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416:542–545.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J. A. and Odorico, J. S. (2000) Human embryonic stem cell and embryonic germ cell lines. TIBTECH 18:53–57.

    Article  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., Coles, B. L. K., Chiasson, B. J., et al. (2000) Retinal stem cells in the adult mammalian eye. Science 287:2032–2036.

    Article  PubMed  CAS  Google Scholar 

  • Wakayama, T., Tabar, V., Rodriguez, I., Perry, A. C. F., Studer, L., and Mombaerts, P. (2001) Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 292: 740–743.

    Article  PubMed  CAS  Google Scholar 

  • Xu, X., Weinstein, M., Li, C., et al. (1998) Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125: 753–765.

    PubMed  CAS  Google Scholar 

  • Ying, Q., Nichols, J., Evans, E. P., and Smith, A. G. (2002) Changing potency by spontaneous fusion. Nature 416:545–548.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Papaioannou, V.E., Hadjantonakis, AK. (2004). Stem Cells from Early Mammalian Embryos. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-411-5_2

  • 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