From fibroblasts and stem cells: implications for cell therapies and somatic cloning
Wilfried A. Kues A B , Joseph W. Carnwath A and Heiner Niemann A
+ Author Affiliations
- Author Affiliations
A Department of Biotechnology, Institut für Tierzucht, Mariensee, D-31535 Neustadt, Germany.
B Corresponding author. Email: kues@tzv.fal.de
Reproduction, Fertility and Development 17(2) 125-134 https://doi.org/10.1071/RD04118
Submitted: 1 August 2004 Accepted: 1 October 2004 Published: 1 January 2005
Abstract
Pluripotent embryonic stem cells (ESCs) from the inner cell mass of early murine and human embryos exhibit extensive self-renewal in culture and maintain their ability to differentiate into all cell lineages. These features make ESCs a suitable candidate for cell-replacement therapy. However, the use of early embryos has provoked considerable public debate based on ethical considerations. From this standpoint, stem cells derived from adult tissues are a more easily accepted alternative. Recent results suggest that adult stem cells have a broader range of potency than imagined initially. Although some claims have been called into question by the discovery that fusion between the stem cells and differentiated cells can occur spontaneously, in other cases somatic stem cells have been induced to commit to various lineages by the extra- or intracellular environment. Recent data from our laboratory suggest that changes in culture conditions can expand a subpopulation of cells with a pluripotent phenotype from primary fibroblast cultures. The present paper critically reviews recent data on the potency of somatic stem cells, methods to modify the potency of somatic cells and implications for cell-based therapies.
Extra keywords: cell fusion, fate change, lineage commitment, reprogramming.
Acknowledgment
The authors acknowledge funding by the Deutsche Forschungsgemeinschaft (DFG).
References
Anderson, R. , Copeland, T. K. , Scholer, H. , Heasman, J. , and Wylie, C. (2000). The onset of germ cell migration in the mouse embryo. Mech. Dev. 91, 61–68.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Anger, M. , Kues, W. A. , Klima, J. , Mielenz, M. , Kubelka, M. , Motlik, J. , Esner, M. , Dvorak, P. , Carnwath, J. W. , and Niemann, H. (2003). Cell cycle dependent expression of Plk1 in synchronized porcine fetal fibroblasts. Mol. Reprod. Dev. 65, 245–253.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Bailey, P. , Holowacz, T. , and Lassar, A. B. (2001). The origin of skeletal muscle stem cells in the embryo and the adult. Curr. Opin. Cell Biol. 13, 679–689.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Balsam, L. B. , Wagers, A. J. , Christensen, J. L. , Kofidis, T. , Weissman, I. L. , and Robbins, R. C. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428, 668–673.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Baron, F. , and Storb, R. (2004). Allogeneic hematopoietic stem cell transplantation as treatment for hematological malignancies: a review. Springer Semin. Immunopathol. ,In press.
Bjornson, C. , Rietze, R. L. , Reynolds, B. A. , Magli, M. C. , and Vescovi, A. L. (1999). Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283, 534–537.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Boiani, M. , Eckardt, S. , Scholer, H. R. , and McLaughlin, K. J. (2002). Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes Dev. 16, 1209–1219.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Brambrink, T. , Wabnitz, P. , Halter, R. , Klocke, R. , Carnwath, J. W. , Kues, W. , Wrenzycki, C. , Paul, D. , and Niemann, H. (2002). Application of cDNA arrays to monitor mRNA profiles in single preimplantation mouse embryos. Biotechniques 33, 376–378.
| PubMed |
Brenner, C. A. , Barritt, J. A. , Willadsen, S. , and Cohen, J. (2000). Mitochondrial DNA heteroplasmy after human ooplasmic transplantation. Fertil. Steril. 74, 573–578.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Camargo, F. D. , Green, R. , Capetenaki, Y. , Jackson, K. A. , and Goodell, M. A. (2003). Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat. Med. 9, 1520–1527.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cameron, H. A. , and McKay, R. (1998). Stem cells and neurogenesis in the adult brain. Curr. Opin. Neurobiol. 8, 677–680.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Caplan, A. I. , and Bruder, S. P. (2001). Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol. Med. 7, 259–264.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Castro, R. F. , Jackson, K. A. , Goodell, M. A. , Robertson, C. S. , Liu, H. , and Shine, H. D. (2002). Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 297, 1299.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chang, H. Y. , Chi, J. T. , Dudoit, S. , Bondre, C. , van de Rijn, M. , Botstein, D. , and Brown, P. O. (2002). Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc. Natl Acad. Sci. USA 99, 12 877–12 882.
| Crossref | GoogleScholarGoogle Scholar |
Chien, K. R. (2004). Lost in translation. Nature 428, 607–608.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Clarke, D. L. , Johansson, C. B. , Wilbertz, J. , Veress, B. , Nilsson, E. , Karlstrom, H. , Lendahl, U. , and Frisen, J. (2000). Generalized potential of adult neural stem cells. Science 288, 1660–1663.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cohen, J. , Scott, R. , Alikani, M. , Schimmel, T. , Munne, S. , Levron, J. , Wu, L. , Brenner, C. , Warner, C. , and Willadsen, S. (1998). Ooplasmic transfer in mature human oocytes. Mol. Hum. Reprod. 4, 269–280.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Corbel, S. Y. , Lee, A. , Yi, L. , Duenas, J. , Brazelton, T. R. , Blau, H. M. , and Rossi, F. M. (2003). Contribution of hematopoietic stem cells to skeletal muscle. Nat. Med. 9, 1528–1532.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Eggan, K. , Baldwin, K. , Tackett, M. , Osborne, J. , Gogos, J. , Chess, A. , Axel, R. , and Jaenisch, R. (2004). Mice cloned from olfactory sensory neurons. Nature 428, 44–49.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Eglitis, M. A. , and Mezey, E. (1997). Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc. Natl Acad. Sci. USA 94, 4080–4085.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ferrari, G. , Cusella-De Angelis, G. , Coletta, M. , Paolucci, E. , Stornaiuolo, A. , Cossu, G. , and Mavilio, F. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gage, F. (2000). Mammalian neural stem cells. Science 287, 1433–1438.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gimble, J. , and Guilak, F. (2003). Adipose-derived adult stem cells: isolation, characterization, and differentiation potenial. Cytotherapy 5, 362–369.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Goodell, M. A. , Brose, K. , Paradis, G. , Conner, A. S. , and Mulligan, R. C. (1996). Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 183, 1797–1806.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gritti, A. , Parati, E. A. , Cova, L. , Frolichsthal, P. , and Galli, R. , et al. (1996). Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor. J. Neurosci. 16, 1091–1100.
| PubMed |
Hakelien, A. M. , Landsverk, H. B. , Robl, J. M. , Skalhegg, B. S. , and Collas, P. (2002). Reprogramming fibroblasts to express T-cell functions using cell extracts. Nat. Biotechnol. 20, 460–466.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hakelien, A. M. , Gaustad, K. G. , and Collas, P. (2004). Transient alteration of cell fate using a nuclear and cytoplasmic extract of an insulinoma cell line. Biochem. Biophys. Res. Commun. 316, 834–841.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Han, X. , and Amar, S. (2002). Identification of genes differentially expressed in cultured human periodontal ligament fibroblasts vs. human gingival fibroblasts by DNA microarray analysis. J. Dent. Res. 81, 399–405.
| PubMed |
Hochedlinger, K. , and Jaenisch, R. (2002). Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 415, 1035–1038.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Humpherys, D. , Eggan, K. , Akutsu, H. , Hochedlinger, K. , Rideout, W. M. , Biniszkiewicz, D. , Yanagimachi, R. , and Jaenisch, R. (2001). Epigenetic instability in ES cells and cloned mice. Science 293, 95–97.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Jackson, K. A. , Majka, S. M. , Wang, H. , Pocius, J. , Hartley, C. J. , Majesky, M. W. , Entman, M. L. , Michael, L. H. , Hirschi, K. K. , and Goodell, M. A. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107, 1395–1402.
| PubMed |
Jaenisch, R. , Eggan, K. , Humpherys, D. , Rideout, W. , and Hochedlinger, K. (2002). Nuclear cloning, stem cells, and genomic reprogramming. Cloning Stem Cells 4, 389–396.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Jiang, Y. , Jahagirdar, B. N. , Reinhardt, R. L. , Schwartz, R. E. , and Keene, C. D. , et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41–49.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Johnson, J. , Canning, J. , Kaneko, T. , Pru, J. K. , and Tilly, J. L. (2004). Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428, 145–150.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kablar, B. , Tajbakhsh, S. , and Rudnicki, M. A. (2000). Transdifferentiation of esophageal smooth to skeletal muscle is myogenic bHLH factor-dependent. Development 127, 1627–1639.
| PubMed |
Kang, Y. K. , Koo, D. B. , Park, J. S. , Choi, Y. H. , Kim, H. N. , Chang, W. K. , Lee, K. K. , and Han, Y. M. (2001). Typical demethylation events in cloned pig embryos. Clues on species-specific differences in epigenetic reprogramming of a cloned donor genome. J. Biol. Chem. 276, 39 980–39 984.
| Crossref | GoogleScholarGoogle Scholar |
Kang, Y. K. , Park, J. S. , Koo, D. B. , Choi, Y. H. , Kim, S. U. , Lee, K. K. , and Han, Y. M. (2002). Limited demethylation leaves mosaic-type methylation states in cloned bovine pre-implantation embryos. EMBO J. 21, 1092–1100.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kopen, G. C. , Prockop, D. J. , and Phinney, D. G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc. Natl Acad. Sci. USA 96, 10 711–10 716.
| Crossref | GoogleScholarGoogle Scholar |
Kues, W. A. , and Niemann, H. (2004). The contribution of farm animals to human health. Trends Biotechnol. 22, 286–294.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kues, W. A. , Anger, M. , Carnwath, J. W. , Paul, D. , Motlik, J. , and Niemann, H. (2000). Cell cycle synchronization of porcine fetal fibroblasts. Effects of serum deprivation and reversible cell cycle inhibitors. Biol. Reprod. 62, 412–419.
| PubMed |
Kues, W. A. , Carnwath, J. W. , Paul, D. , and Niemann, H. (2002). Cell cycle synchronization of porcine fetal fibroblasts by serum deprivation initites an unconventional form of apoptosis. Cloning Stem Cells 4, 231–243.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
LaBarge, M. A. , and Blau, H. M. (2002). Biological progression from adult bone marrow to mononucleated muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111, 589–601.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lagasse, E. , Connors, H. , Al-Dhalimy, M. , Reitsma, M. , Dohse, M. , Osborne, L. , Wang, X. , Finegold, M. , Weissman, I. L. , and Grompe, M. (2000). Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6, 1229–1234.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Landsverk, H. B. , Hakelien, A. M. , Kuntziger, T. , Robl, J. M. , Skalhegg, B. S. , and Collas, P. (2002). Reprogrammed gene expression in a somatic cell-free extract. EMBO Rep. 3, 384–389.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lin, Y. , Weisdorf, D. J. , Solovey, A. , and Hebbel, R. P. (2000). Origins of circulating endothelial cells and endothelial outgrowth from blood. J. Clin. Invest. 105, 71–77.
| PubMed |
Malter, H. E. , and Cohen, J. (2002). Ooplasmic transfer: animal models assist human studies. Reprod. Biomed. Online 5, 26–35.
Minguell, J. J. , Erices, A. , and Conget, P. (2001). Mesenchymal stem cells. Exp. Biol. Med. 226, 507–520.
Morshead, C. M. , Benveniste, P. , Iscove, N. N. , and van der Kooy, D. (2002). Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat. Med. 8, 268–273.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Moulin, V. , Garrel, D. , Auger, F. A. , O'Connor-McCourt, M. , Castilloux, G. , and Germain, L. (1999). What's new in human wound-healing myofibroblasts? Curr. Top. Pathol. 93, 123–133.
| PubMed |
Murry, C. E. , Soonpaa, M. H. , Reinecke, H. , Nakajima, H. , and Nakajima, H. O. , et al. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428, 664–668.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Niemann, H. , and Kues, W. A. (2003). Application of transgenesis in livestock for agriculture and biomedicine. Anim. Reprod. Sci. 79, 291–317.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Niemann, H. , and Wrenzycki, C. (2000). Alterations of expression of developmentally important genes in preimplantation bovine embryos by in vitro culture conditions: implications for subsequent development. Theriogenology 53, 21–24.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Niemann, H. , Wrenzycki, C. , Lucas-Hahn, A. , Brambrink, T. , Kues, W. A. , and Carnwath, J. W. (2002). Gene expression patterns in bovine in vitro-produced and nuclear transfer-derived embryos and their implications for early development. Cloning Stem Cells 4, 29–38.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nilsson, S. K. , and Simmons, P. J. (2004). Transplantable stem cells: home to specific niches. Curr. Opin. Hematol. 11, 102–106.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Oback, B. , and Wells, D. (2002). Donor cells for nuclear cloning: many are called, but few are chosen. Cloning Stem Cells 4, 147–168.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Orlic, D. , Kajstura, J. , Chimenti, S. , Jakoniuk, I. , and Anderson, S. M. , et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature 410, 701–705.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Patapoulian, A. , Wold, B. J. , and Wagner, R. A. (1995). Evidence for developmentally programmed transdifferentiation in mouse esphageal muscle. Science 270, 1818–1821.
| PubMed |
Paterson, L. , DeSousa, P. , Ritchie, W. , King, T. , and Wilmut, I. (2003). Application of reproductive biotechnology in animals: implications and potentials. Applications of reproductive cloning. Anim. Reprod. Sci. 79, 137–143.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Petersen, B. E. , Bowen, W. C. , Patrene, K. D. , Mars, W. M. , Sullivan, A. K. , Murase, N. , Boggs, S. S. , Greenberger, J. S. , and Goff, J. P. (1999). Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Pesce, M. , and Schöler, H. R. (2001). Oct-4: Gatekeeper in the beginnings of mammalian development. Stem Cells 19, 271–278.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Powell, A. M. , Talbot, N. C. , Wells, K. D. , Kerr, D. E. , Pursel, V. G. , and Wall, R. J. (2004). Cell donor influences success of producing cattle by somatic cell nuclear transfer. Biol. Reprod. 71, 210–216.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Prather, R. S. , Hawley, R. J. , Carter, D. B. , Lai, L. , and Greenstein, J. L. (2003). Transgenic swine for biomedicine and agriculture. Theriogenology 59, 115–123.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Priller, J. , Persons, D. A. , Klett, F. F. , Kempermann, G. , Kreutzberg, G. W. , and Dirnagl, U. (2001). Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo. J. Cell Biol. 155, 733–738.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Qi, X. , Li, T.-G. , Hao, J. , Hu, J. , Wang, J. , Simmons, H. , Miura, S. , Mishina, Y. , and Zhao, G.-Q. (2004). BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proc. Natl Acad. Sci. USA 101, 6027–6032.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Raff, M. (2003). Adult stem cell plasticity: fact or artifact? Annu. Rev. Cell Dev. Biol. 19, 1–22.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Reynolds, B. A. , and Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian nervous system. Science 255, 1707–1710.
| PubMed |
Rideout, W. M. , Wakayama, T. , Wutz, A. , Eggan, K. , Jackson-Grusby, L. , Dausman, J. , Yanagimachi, R. , and Jaenisch, R. (2000). Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat. Genet. 24, 109–110.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Rossant, J. (2001). Stem cells from the mammalian blastocyst. Stem Cells 19, 477–482.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Schaetzlein, S. , Lucas-Hahn, A. , Lemme, E. , Kues, W. A. , Dorsch, M. , Manns, M. P. , Niemann, H. , and Rudolph, K. L. (2004). Telomere length is reset during early mammalian embryogenesis. Proc. Natl Acad. Sci. USA 101, 8034–8038.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Smith, A. G. (2001). Embryo-derived stem cells of mice and men. Annu. Rev. Cell Dev. Biol. 17, 435–462.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Steinborn, R. , Zakhartchenko, V. , Wolf, E. , Muller, M. , and Brem, G. (1998). Non-balanced mix of mitochondrial DNA in cloned cattle produced by cytoplast-blastomere fusion. FEBS Lett. 426, 357–361.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Terada, N. , Hamazaki, T. , Oka, M. , Hoki, M. , Mastalerz, D. M. , Nakano, Y. , Meyer, E. M. , Morel, L. , Petersen, B. E. , and Scott, E. W. (2002). Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Theise, N. D. , Badve, S. , Saxena, R. , Henegariu, O. , Sell, S. , Crawford, J. M. , and Krause, D. S. (2000). Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 31, 235–240.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Toma, J. G. , Akhavan, M. , Fernandes, K. J. , Barnabe-Heider, F. , Sadikot, A. , Kaplan, D. R. , and Miller, F. D. (2001). Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 3, 778–784.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Vassilopoulos, G. , Wang, P. R. , and Russell, D. (2003). Transplanted bone marrow forms liver by cell fusion. Nature 422, 901–904.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Verfaillie, C. (2002). Adult stem cells: assessing the case for pluripotency. Trends Cell Biol. 12, 502–508.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wagers, A. J. , Sherwood, R. I. , Christensen, J. L. , and Weissman, I. L. (2002). Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256–2259.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wang, X. , Willenbring, H. , Akkari, Y. , Torimaru, Y. , Foster, M. , Al-Dhalimy, M. , Lagasse, E. , Finegold, M. , Olson, S. , and Grompe, M. (2003). Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897–901.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Weissman, I. L. (2000). Stem cells: units of development, units of regeneration and units of evolution. Cell 100, 157–168.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Weissman, I. L. , Anderson, D. J. , and Gage, F. (2001). Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu. Rev. Cell Dev. Biol. 17, 387–403.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wheeler, M. B. , Walters, E. M. , and Clark, S. G. (2003). Transgenic animals in biomedicine and agriculture: outlook for the future. Anim. Reprod. Sci. 79, 265–289.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wilmut, I. , Schnieke, A. E. , McWhir, J. , Kind, A. J. , and Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wu, A. M. , Till, J. E. , Siminovitch, L. , and McCulloch, E. A. (1967). A cytological study of the capacity for differentiation of normal hematopoietic colony-forming cells. J. Cell. Physiol. 69, 545–548.
Wurmser, A. E. , Nakashima, K. , Summers, R. G. , Toni, N. , D’Amour, K. A. , Lle, D. C. , and Gage, F. H. (2004). Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 430, 350–356.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Yamazaki, Y. , Mann, M. R. , Lee, S. S. , Marh, J. , McCarrey, J. R. , Yanagimachi, R. , and Bartolomei, M. S. (2003). Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc. Natl Acad. Sci. USA 100, 12 207–12 212.
| Crossref | GoogleScholarGoogle Scholar |
Yeom, Y. I. , Fuhrmann, G. , Ovitt, C. E. , Brehm, A. , Ohbo, K. , Gross, M. , Hubner, K. , and Scholer, H. R. (1996). Germline regulatory element of Oct4 specific for the totipotent cycle of embryonal cells. Development 122, 881–894.
| PubMed |
Ying, Q. L. , Nichols, J. , Evans, E. P. , and Smith, A. G. (2002). Changing potency by spontaneous fusion. Nature 416, 545–548.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Young, L. E. , and Beaujean, N. (2004). DNA methylation in the preimplantation embryo: the differing stories of the mouse and sheep. Anim. Reprod. Sci. 82–83, 61–78.
| Crossref | GoogleScholarGoogle Scholar |
Young, L. E. , Sinclair, K. D. , and Wilmut, I. (1998). Large offspring syndrome in cattle and sheep. Rev. Reprod. 3, 155–163.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zakhartchenko, V. , Durcova-Hills, G. , Schernthaner, W. , Stojkovic, M. , and Reichenbach, H. D. , et al. (1999). Potential of fetal germ cells for nuclear transfer in cattle. Mol. Reprod. Dev. 52, 421–426.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zuk, P. A. , Zhu, M. , Ashjian, P. , De Ugarte, D. A. , Huang, J. I. , Mizino, H. , Alfonso, Z. C. , Fraser, J. K. , Benhaim, P. , and Hedrick, M. H. (2002). Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279–4295.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
