ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal Via the PI3K/AKT Pathway
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ABSTRACT: ELABELA (ELA) is a peptide hormone required for heart development that signals via the Apelin Receptor (APLNR, APJ). ELA is also abundantly secreted by human embryonic stem cells (hESCs), which do not express APLNR. Here we show that ELA signals in a paracrine fashion in hESCs to maintain self-renewal. ELA inhibition by CRISPR/Cas9-mediated deletion, shRNA or neutralizing antibodies causes reduced hESC growth, cell death and loss of pluripotency. Global phosphoproteomic and transcriptomic analyses of ELA-pulsed hESCs show that it activates PI3K/AKT/mTORC1 signaling required for cell survival. ELA promotes hESC cell cycle progression and protein translation, and blocks stress-induced apoptosis. INSULIN and ELA have partially overlapping functions in hESC medium, but only ELA can potentiate
ORGANISM(S): Homo sapiens
SUBMITTER: Lena Ho
PROVIDER: E-GEOD-71949 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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