Pluripotency can be induced in differentiated mouse and human cells by expressing Oct4 along with various combinations of other transcription factors (Park et al., AC220 research buy 2008, Stadtfeld and Hochedlinger, 2010, Takahashi et al., 2007, Takahashi and Yamanaka, 2006 and Yu et al., 2007). These induced pluripotent stem (iPS) cells resemble ES

cells in terms of gene expression, cell-cycle regulation, teratoma formation, and metabolic regulation (Prigione et al., 2010 and Stadtfeld and Hochedlinger, 2010). Importantly, mouse iPS cells have the ability to generate a viable adult mouse upon injection into blastocysts (Boland et al., 2009 and Zhao et al., 2009). This means that all of the aspects of cellular physiology that are necessary for pluripotent cells to differentiate into normal specialized cells can be induced by these transcription factors. On the other hand, recent studies have identified epigenetic aberrations in iPS cells that indicate that these cells are often not fully reprogrammed to a normal pluripotent state (Kim et al., 2010 and Lister et al., 2011). This raises the questions of whether some PD0332991 clinical trial differences in cellular physiology, or at least epigenetic state, are regulated independently of the transcriptional network and whether these differences might stabilize the pluripotent state. Tissue-specific stem cells depend on transcription

factors that regulate stem cell self-renewal but not restricted progenitor proliferation. The Sox17 transcription factor is required for the maintenance of fetal and neonatal HSCs but is not expressed by the vast majority of restricted progenitors in the hematopoietic system (Kim et al., 2007). Sox17 is not expressed by neural stem cells, but other Sox family transcription factors likely perform similar functions in neural stem cells. Sox2 and Sox9 are required by CNS stem cells during fetal development, as well as in the adult brain (Avilion et al., 2003, Favaro et al., 2009, because Graham et al., 2003 and Scott et al., 2010). Sox10 is required to maintain neural crest stem cells during peripheral nervous system (PNS)

development but is not required by the restricted neuronal progenitors that arise from these cells (Kim et al., 2003). Different Sox family members are therefore required to maintain undifferentiated stem cells in different tissues during fetal development. Prdm family transcription factors are also required by stem cells in multiple tissues. Prdm14 is required by primordial germ cells and stabilizes ES pluripotency (Chia et al., 2010 and Yamaji et al., 2008). Prdm1/Blimp1 is required for primordial germ cells and progenitors in the sebaceous gland (Horsley et al., 2006 and Ohinata et al., 2005). Prdm16 is required by stem cells in the hematopoietic and nervous systems, but not by most restricted progenitors in the same tissues (Chuikov et al., 2010).