Prostaglandin E₂ Is Required for BMP4-Induced Mesoderm Differentiation of Human Embryonic Stem Cells.

ABSTRACT: The accurate control of early cell fate specification during differentiation of human embryonic stem cells (hESCs) is critical for acquiring pure therapeutic cell populations of interest. Bone morphogenetic protein 4 (BMP4) is a key mesoderm inducer from ESCs. However, the molecular mechanism of the mesodermal cell fate decision induced by BMP4 remains unclear. Here, we demonstrate the requirement of a bioactive lipid, prostaglandin E₂ (PGE₂), for the mesoderm specification from hESCs by BMP4 induction. We show that BMP4 directly regulates the expression of the key enzyme for PGE₂ synthesis, COX-1, and promotes PGE₂ production. More importantly, in the absence of BMP4, forced COX-1 expression or PGE₂ treatment is sufficient to initiate mesoderm specification of hESCs by activation of EP2-PKA signaling and modulation of nuclear translocation of ?-catenin. Together, our findings provide insights into the critical role of BMP regulation of PGE₂ synthesis and its downstream signaling in initiating mesoderm commitment of hESCs.

SUBMITTER: Zhang B 

PROVIDER: S-EPMC5919771 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature