IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
Activins
/ metabolism
Animals
Blastocyst
/ metabolism
Cell Differentiation
/ drug effects
Cell Self Renewal
/ physiology
Cells, Cultured
Coculture Techniques
Culture Media
/ chemistry
Endoderm
/ cytology
Extraembryonic Membranes
/ cytology
Fibroblasts
/ cytology
Gene Expression Regulation, Developmental
Human Embryonic Stem Cells
/ cytology
Humans
Induced Pluripotent Stem Cells
/ cytology
Insulin-Like Growth Factor I
/ metabolism
Mice
Phosphatidylinositol 3-Kinases
/ metabolism
Receptor, IGF Type 1
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
Transcriptome
X Chromosome Inactivation
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 02 2020
07 02 2020
Historique:
received:
20
05
2019
accepted:
23
01
2020
entrez:
9
2
2020
pubmed:
9
2
2020
medline:
19
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32034154
doi: 10.1038/s41467-020-14629-x
pii: 10.1038/s41467-020-14629-x
pmc: PMC7005693
doi:
Substances chimiques
Culture Media
0
IGF1 protein, human
0
IGF1R protein, human
0
Activins
104625-48-1
Insulin-Like Growth Factor I
67763-96-6
MTOR protein, human
EC 2.7.1.1
Receptor, IGF Type 1
EC 2.7.10.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
764Subventions
Organisme : Medical Research Council
ID : MC_UP_1202/9
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001070
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001120
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001070
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001070
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 103799/Z/14/Z
Pays : International
Organisme : Medical Research Council
ID : MC_PC_17179
Pays : United Kingdom
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_PC_16062 10609
Pays : International
Organisme : Wellcome Trust
ID : FC001120
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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