ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway

ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway
Title:
ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway
Other Titles:
Cell Stem Cell
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Publication Date:
17 September 2015
Citation:
Lena Ho, Shawn Y.X. Tan, Sheena Wee, Yixuan Wu, Sam J.C. Tan, Navin B. Ramakrishna, Serene C. Chng, Srikanth Nama, Iwona Szczerbinska, Yun-Shen Chan, Stuart Avery, Norihiro Tsuneyoshi, Huck Hui Ng, Jayantha Gunaratne, N. Ray Dunn, Bruno Reversade, ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway, Cell Stem Cell, Volume 17, Issue 4, 1 October 2015, Pages 435-447, ISSN 1934-5909, http://dx.doi.org/10.1016/j.stem.2015.08.010.
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 the TGFβ pathway to prime hESCs toward the endoderm lineage. We propose that ELA, acting through an alternate cell-surface receptor, is an endogenous secreted growth factor in human embryos and hESCs that promotes growth and pluripotency.
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ISSN:
1934-5909
1875-9777
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