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IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.

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journal contribution
posted on 13.02.2020 by Sissy E Wamaitha, Katarzyna J Grybel, Gregorio Alanis-Lobato, Claudia Gerri, Sugako Ogushi, Afshan McCarthy, Shantha K Mahadevaiah, Lyn Healy, Rebecca A Lea, Miriam Molina-Arcas, Liani G Devito, Kay Elder, Phil Snell, Leila Christie, Julian Downward, James MA Turner, Kathy K Niakan
Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human embryo and identify expression for the insulin and insulin growth factor 1 (IGF1) receptors, along with IGF1 ligand. Consequently, we generate a minimal chemically-defined culture medium in which IGF1 together with Activin maintain self-renewal in the absence of fibroblast growth factor (FGF) signalling. Under these conditions, we derive several pluripotent stem cell lines that express pluripotency-associated genes, retain high viability and a normal karyotype, and can be genetically modified or differentiated into multiple cell lineages. We also identify active phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling in early human embryos, and in both primed and naïve pluripotent culture conditions. This demonstrates that signalling insights from human blastocysts can be used to define culture conditions that more closely recapitulate the embryonic niche.

Funding

Crick (Grant ID: 10193, Grant title: Turner FC001193) Crick (Grant ID: 10120, Grant title: Niakan FC001120) Crick (Grant ID: 10070, Grant title: Downward FC001070) Wellcome Trust (Grant ID: 103799/Z/14/Z, Grant title: WT 103799/Z/14/Z)

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