10779/crick.11843277.v1
Sissy E Wamaitha
Sissy E
Wamaitha
Katarzyna J Grybel
Katarzyna J
Grybel
Gregorio Alanis-Lobato
Gregorio
Alanis-Lobato
Claudia Gerri
Claudia
Gerri
Sugako Ogushi
Sugako
Ogushi
Afshan McCarthy
Afshan
McCarthy
Shantha K Mahadevaiah
Shantha K
Mahadevaiah
Lyn Healy
Lyn
Healy
Rebecca A Lea
Rebecca A
Lea
Miriam Molina-Arcas
Miriam
Molina-Arcas
Liani G Devito
Liani G
Devito
Kay Elder
Kay
Elder
Phil Snell
Phil
Snell
Leila Christie
Leila
Christie
Julian Downward
Julian
Downward
James MA Turner
James MA
Turner
Kathy K Niakan
Kathy K
Niakan
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
The Francis Crick Institute
2020
Turner FC001193
Niakan FC001120
Downward FC001070
LM-ack
FC-ack
HTS-ack
CB-ack
SC-ack
HESC
2020-02-13 14:04:37
Journal contribution
https://crick.figshare.com/articles/journal_contribution/IGF1-mediated_human_embryonic_stem_cell_self-renewal_recapitulates_the_embryonic_niche_/11843277
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.