IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
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Date
2020-02-07ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Cells, Cultured
Fibroblasts
Blastocyst
Endoderm
Animals
Humans
Mice
Activins
Receptor, IGF Type 1
Insulin-Like Growth Factor I
Culture Media
Coculture Techniques
Signal Transduction
Cell Differentiation
Gene Expression Regulation, Developmental
Extraembryonic Membranes
X Chromosome Inactivation
Induced Pluripotent Stem Cells
Phosphatidylinositol 3-Kinases
TOR Serine-Threonine Kinases
Transcriptome
Human Embryonic Stem Cells
Cell Self Renewal
Research team
Lung Cancer Group
Language
eng
Date accepted
2020-01-23
License start date
2020-02-07
Citation
Nature communications, 2020, 11 (1), pp. 764 - ?