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Cell Stem Cell. 2015 Oct 1;17(4):435-47. doi: 10.1016/j.stem.2015.08.010. Epub 2015 Sep 17.

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

Author information

1
Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648. Electronic address: lena.ho@reversade.com.
2
Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648.
3
Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673.
4
Genome Institute of Singapore, A(∗)STAR, Singapore 138672.
5
Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673. Electronic address: bruno@reversade.com.

Erratum in

  • Cell Stem Cell. 2015 Nov 5;17(5):635. Sczerbinska, Iwona [corrected to Szczerbinska, Iwona].

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.

PMID:
26387754
DOI:
10.1016/j.stem.2015.08.010
[Indexed for MEDLINE]
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