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.