Keeping an eye on retinoblastoma control of human embryonic stem cells

Department of Pediatrics, Stanford Medical School, Stanford, California 94305, USA.
Journal of Cellular Biochemistry (Impact Factor: 3.37). 12/2009; 108(5):1023-30. DOI: 10.1002/jcb.22342
Source: PubMed

ABSTRACT Human embryonic stem cells (hESCs) hold great promise in regenerative medicine. However, before the full potential of these cells is achieved, major basic biological questions need to be addressed. In particular, there are still gaps in our knowledge of the molecular mechanisms underlying the derivation of hESCs from blastocysts, the regulation of the undifferentiated, pluripotent state, and the control of differentiation into specific lineages. Furthermore, we still do not fully understand the tumorigenic potential of hESCs, limiting their use in regenerative medicine. The RB pathway is a key signaling module that controls cellular proliferation, cell survival, chromatin structure, and cellular differentiation in mammalian cells. Members of the RB pathway are important regulators of hESC biology and manipulation of the activity of this pathway may provide novel means to control the fate of hESCs. Here we review what is known about the expression and function of members of the RB pathway in hESCs and discuss areas of interest in this field.

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Available from: Julien Sage, Aug 10, 2015
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    • "Notably, no significant change in the growth rate of the 4F-infected MEFs was observed upon Rb knockdown (Figure 2A), as was previously observed in Rb-deficient MEFs (Dannenberg et al., 2000; Sage et al., 2000) (see below). Similarly, there was no change in the S phase fraction in the shRb-infected MEFs, although, at day 6 there was a trend to a longer G2 and shorter G1 (Figures 2B and 2C, Figure S2A), possibly a consequence of increased reprogramming because a shorter G1 correlates with the acquisition of pluripotency (Conklin and Sage, 2009). Annexin V staining did not show a significant difference in apoptosis (Figure 2D, Figure S2B). "
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    • "In mESCs, pRb is permanently inactivated by hyperphosphorylation , leading to constitutive activity of E2F TFs, which in turn allows an R-point-independent short transition through G1 phase (Savatier et al. 1994; Stead et al. 2002). Although differences were observed when compared with mESCs (Conklin and Sage 2009), similar mechanisms are presumed to regulate human ESCs (hESCs). "
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