ESPEYB17 4. Growth and Growth Factors New paradigms (3 abstracts)
4.13. IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche
Wamaitha SE , Grybel KJ , Alanis-Lobato G , Gerri C , Ogushi S , AMcCarthy A , Mahadevaiah SK , Healy L , Lea RA , Molina-Arcas M , Devito LG , Elder K , Snell P , Christie L , Downward J , Turner JMA & Niakan KK
Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, UK Kathy.niakan@crick.ac.uk
To read the full abstract: Nat Commun. 2020 Feb 7;11(1):764.
The signaling pathways involved in the regulation of early human development are largely unknown and the IGF system has been proposed to play a major role (1). The knowledge of mechanisms and actors involved in early life development is crucial to develop successful strategies for maintaining pluripotent human embryonic stem cells (hESCs).
This sophisticated study performed a comprehensive analysis of signaling associated transcripts expressed in human preimplantation embryos. IGF-I ligand and the IGF-I and insulin receptors were found expressed in the human extraembryonic primitive endoderm (PE) and in pluripotent epiblast (EPI) cells, respectively. A minimal chemically-defined culture medium characterized by the supplementation of IGF-I together with Activin (AI medium) instead of fibroblast growth factor (FGF) was developed and evaluated. This medium was effective to derive hESCs from embryos, as well as induced pluripotent stem cells (iPSCs) reprogrammed from fibroblasts. AI-cultured hESCs exhibited a transcriptional expression profile similar to hESCs cultured under conventional conditions, retained the ability to differentiate into a variety of cell types, and were able to be genetically modified using CRISPR/Cas9 mutagenesis. IGF-I affected hESC self-renewal by acting on downstream PI3K signaling pathway and exerted a proliferative effect on the inner cell mass of the human embryo.
These results shed light on the signaling pathways involved in early stages of human embryo development and demonstrates the possibility of using an easily reproducible medium to culture hESCs. At the same time, this study raises many doubts about the ethics of experiments on human embryos. The Editors of this chapter dissociate morally from this approach based on manipulation of human life, though at embryo stage.
Reference:
1. Spanos S, Becker DL, Winston RM, Hardy K. Anti-apoptotic action of insulin-like growth factor-I during human preimplantation embryo development. Biol Reprod. 2000;63(5):1413–20.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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