Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells.

ABSTRACT: During embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent way. Yet, in mammalian embryos, concentrations change rapidly compared to the time for making cell fate decisions. Here, we use human embryonic stem cells (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. We show that BMP4 response is concentration dependent, but that expression of many Nodal targets depends on rate of concentration change. Moreover, in a self-organized stem cell model for human gastrulation, expression of these genes follows rapid changes in endogenous Nodal signaling. Our study shows a striking contrast

SUBMITTER: Heemskerk I 

PROVIDER: S-EPMC6398983 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature