Differentiation of embryonic stem cells is induced by GATA factors

Abstract

Extraembryonic endoderm (ExE) is differentiated from the inner cell mass of the late blastocyst-stage embryo to form visceral and parietal endoderm, both of which have an important role in early embryogenesis. The essential roles of Gata-6 and Gata-4 on differentiation of visceral endoderm have been identified by analyses of knockout mice. Here we report that forced expression of either Gata-6 or Gata-4 in embryonic stem (ES) cells is sufficient to induce the proper differentiation program towards ExE. We believe that this is the first report of a physiological differentiation event induced by the ectopic expression of a transcription factor in ES cells.

Cell and molecular regulation of the mouse blastocyst

“…These studies have been complemented by studies on Gata6 in ES cells. Overexpression of Gata4/6 in ES cells also leads to differentiation into a PE-like cells and down-regulation of the ICM/EPI marker Oct4 (Fujikura et al, 2002). Thus, antagonism between Nanog and Gata factors may reinforce XEN and ES cell fates to promote self-renewal and prevent switching among these lineages, analogous to the activity of Oct4 and Cdx2 in ES and TS cell fates (Fig.…”

“…Evidence from in vitro studies suggests that EPI and PE cells acquire different adhesive characteristics that allow them to sort out from each other. In ES cells, Gata4/6 overexpression leads to a strong up-regulation of LamininB1, which changes the adhesion properties of Gata-expressing cells (Fujikura et al, 2002). Mutation of Dab2, a direct target of Gata6 (Morrisey et al, 2000) seems to cause a defect in the sorting out process in vivo.…”

Self-renewal of teratocarcinoma and embryonic stem cells

“…These molecules are unique to date in their ability to cause ES cells to differentiate in an apparently uniform manner. An interesting feature of the differentiation induced by GATA4 and GATA6 is the positive feedback on the endogenous gene expression seen when either transcription factor is exogenously expressed in ES cells (Fujikura et al, 2002). Both GATA4 and GATA6 are also expressed, albeit at a lower level, following supertransfection of ES cells with either Oct4 or STAT3F.…”

“…Transcription factors that have been demonstrated to induce ES cell differentiation into primitive endoderm are GATA6 and GATA4 (Fujikura et al, 2002). These molecules are unique to date in their ability to cause ES cells to differentiate in an apparently uniform manner.…”

L’embryogenèse précoce des mammifères

“…(Figure 2). La surexpression des gènes Gata4 ou Gata6 dans les cellules ES induit leur différenciation en EPr [28,29], montrant que ces gènes ont un impact fort dans l'induction de ce lignage. Dans ces expériences, l'expression des marqueurs de pluripotence diminue rapidement, suggérant des mécanismes de répression active.…”