The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo
Citations Over Time
Abstract
The separation of embryonic from extra-embryonic tissues within the inner cell mass to generate the epiblast (EPI), which will form the new organism, from the primitive endoderm (PE), which will form the yolk sac, is a crucial developmental decision. Here, we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos, with higher expression levels in the inner cell mass progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE. This phenotype can be rescued by simultaneous depletion of both Satb1 and Satb2, owing to their antagonistic effect on the pluripotency regulator Nanog. Consequently, increasing Satb1 expression leads to differentiation into PE and a decrease in EPI, as a result of the modulation of expression of several pluripotency- and differentiation-related genes by Satb1. Finally, we show that Satb1 is a downstream target of the Fgf signalling pathway, linking chromatin modification and Fgf signalling. Together, these results identify a role for Satb1 in the lineage choice between pluripotency and differentiation and further our understanding of early embryonic lineage segregation.
Related Papers
- → The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells(2003)3,186 cited
- → Control of ground-state pluripotency by allelic regulation of Nanog(2012)233 cited
- → NANOG initiates epiblast fate through the coordination of pluripotency genes expression(2022)54 cited
- → Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast(2014)38 cited
- → A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos(2019)38 cited