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ELABELA helps unlock the secrets of early survival and development

5 Apr 2016

A newly discovered hormone has a vital role in survival and differentiation of human embryonic stem cells

A*STAR researchers have discovered a new hormone that plays a role in the fate of human embryonic stem cells.

A*STAR researchers have discovered a new hormone that plays a role in the fate of human embryonic stem cells.

© Science Photo Library – STEVE GSCHMEISSNER/Brand X Pictures/Getty

The secret to why human embryonic stem cells are able to self-renew and develop may be revealed by the discovery of a new hormone.

The peptide hormone known as ELABELA (ELA) has been shown, for the first time, to play a key role in both the self-renewal and early cell differentiation. This finding could pave the way toward new advances in regenerative medicine or cancer treatment.

The team from A*STAR Institute of Medical Biology utilized cutting-edge CRISPR gene-editing technology to discover ELA’s role.

Bruno Reversade, who led the team, said ELABELA was one of a small handful of tiny secreted peptides (a mere 32 amino-acids in length) produced by the embryonic stem cells themselves that played the critical role in allowing them to differentiate.

To our knowledge, no hormonal peptide has ever been shown to maintain the self-renewal capacity of human embryonic stem cells, or their ability to differentiate into the three embryonic germ layers, Reversade explained.

The team found the hormone promotes cell-cycle progression and protein translation, prevents cell death during periods of stress, and primes the cell to divide into the very first three layers of different cells that make up the early embryo.

Reversade said the same pathways that ELA activated in stem cells were also implicated in the development of cancer, meaning the research could have implications for cancer research. “This research could also lead to potential therapeutic treatments in clinical areas where ELA is involved, either through administering it or by developing antibodies that can neutralize it,” he said.

Despite the key role it plays in early embryonic development, up until now ELABELA had gone undetected by researchers because its role is similar to another hormone, insulin.

Bruno Reversade's IMB team.

Bruno Reversade’s IMB team.

© 2016 A*STAR Institute of Medical Biology

“Because insulin is routinely used in human embryonic stem cell culture, the effect of the ELA being produced by the cells was masked for a long time,” explained first author of the paper, Lena Ho. “We only discovered it when we were doing a broader analysis of what pathways were activated when we gave the cells exogenous ELA in a very minimal media that did not contain insulin.”

Reversade said new CRISPR/Cas 9 technology – which harnesses techniques used by the immune system of single-celled organisms to edit genetic information – was very important for his team’s research. This technology allowed them to independently verify results gained through traditional techniques and quickly and easily manipulate cell lines and animals.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Medical Biology, the Genome Institute of Singapore and the Institute of Molecular and Cell Biology. For more information about the team’s research, please visit the Human Genetics Embryology webpage.

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References

Ho, L., Tan, S., Wee, S., Wu, Y., Tan, S. J. C. et al. ELABELA is an endogenous growth factor that sustains hESC self-renewal via the PI3K/AKT pathway. Cell Stem Cell 17, 435–447 (2015). | Article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature