Unraveling the transcriptional network controlling ES cell pluripotency

Abstract

Embryonic stem cells (ES cells) are powerful tools for genetic engineering and hold significant potential for regenerative medicine. Recent work provides new insights into ES cell pluripotency and delineates separate transcriptional pathways in ES cells for maintenance of the undifferentiated state and for self-renewal.

Figure 1

A schematic view of the transcriptional pathways involved in self-renewal and blocking differentiation of murine embryonic stem cells. Self-renewal appears to be regulated by two distinct transcriptional pathways, one involving Esrrb, Tcl1 and Tbx3 and a separate pathway involving Nanog, Oct4 and Sox2, with some degree of cross-talk. Differentiation pathways appear to be separately regulated as well. Nanog, Oct4 and Sox2 cooperate to block trophectoderm and endoderm differentiation, whereas Nanog, Sox2, Esrrb, Tcl1 and Tbx3 cooperate to prevent formation of the epiblast. Raised levels of Nanog on its own appear able to compensate for the loss of Esrrb, Tcl1 or Tbx3 for both self-renewal and blocking differentiation.