IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
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ICR Authors
Authors
Wamaitha, SE
Grybel, KJ
Alanis-Lobato, G
Gerri, C
Ogushi, S
McCarthy, A
Mahadevaiah, SK
Healy, L
Lea, RA
Molina-Arcas, M
Devito, LG
Elder, K
Snell, P
Christie, L
Downward, J
Turner, JMA
Niakan, KK
Grybel, KJ
Alanis-Lobato, G
Gerri, C
Ogushi, S
McCarthy, A
Mahadevaiah, SK
Healy, L
Lea, RA
Molina-Arcas, M
Devito, LG
Elder, K
Snell, P
Christie, L
Downward, J
Turner, JMA
Niakan, KK
Document Type
Journal Article
Date
2020-02-07
Date Accepted
2020-01-23
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.
Citation
Nature communications, 2020, 11 (1), pp. 764 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Lung Cancer Group