Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells.

ABSTRACT: During the first stages of embryonic development, the placenta develops under very low oxygen tension (∼1%-2% O₂), so we sought to determine the regulatory role of oxygen in human trophoblast stem cells (hTSCs). We find that low oxygen promotes hTSC self-renewal but inhibits differentiation to syncytiotrophoblast (STB) and extravillous trophoblast (EVT). The transcription factor GCM1 (glial cell missing transcription factor 1) is downregulated in low oxygen, and concordantly, there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC likewise impaired EVT and STB formation. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation.

SUBMITTER: Cinkornpumin JK 

PROVIDER: S-EPMC12143156 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature