Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells.
The past few years have seen remarkable progress in our understanding of embryonic stem cell (ES cell) biology. The necessity of examining human ES cells in culture, coupled with the wealth of genomic data and the multiplicity of cell lines available, has enabled researchers to identify critical conserved pathways regulating self-renewal and identify markers that tightly correlate with the ES cell state. Comparison across species has suggested additional pathways likely to be important in long-term self-renewal of ES cells including heterochronic genes, microRNAs, genes involved in telomeric regulation, and polycomb repressors. In this review, we have discussed information on molecules known to be important in ES cell self-renewal or blastocyst development and highlighted known differences between mouse and human ES cells. We suggest that several additional pathways required for self-renewal remain to be discovered and these likely include genes involved in antisense regulation, microRNAs, as well as additional global repressive pathways and novel genes. We suggest that cross species comparisons using large-scale genomic analysis tools are likely to reveal conserved and divergent paths required for ES cell self-renewal and will allow us to derive ES lines from species and strains where this has been difficult.
Rao
Mahendra
M
Stem Cell Section, Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. raomah@grc.nia.nih.gov
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins
D006131:Growth Inhibitors; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D027701:Organic Cation Transport Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors