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

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 M. A. Turner and Kathy K. Niakan ()
Additional contact information
Sissy E. Wamaitha: The Francis Crick Institute
Katarzyna J. Grybel: The Francis Crick Institute
Gregorio Alanis-Lobato: The Francis Crick Institute
Claudia Gerri: The Francis Crick Institute
Sugako Ogushi: The Francis Crick Institute
Afshan McCarthy: The Francis Crick Institute
Shantha K. Mahadevaiah: The Francis Crick Institute
Lyn Healy: The Francis Crick Institute
Rebecca A. Lea: The Francis Crick Institute
Miriam Molina-Arcas: The Francis Crick Institute
Liani G. Devito: The Francis Crick Institute
Kay Elder: Bourn Hall Clinic, Bourn
Phil Snell: Bourn Hall Clinic, Bourn
Leila Christie: Bourn Hall Clinic, Bourn
Julian Downward: The Francis Crick Institute
James M. A. Turner: The Francis Crick Institute
Kathy K. Niakan: The Francis Crick Institute

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-14629-x

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