Generation and trapping of a mesoderm biased state of human pluripotency.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 10 2020
05 10 2020
Historique:
received:
08
11
2019
accepted:
10
09
2020
entrez:
6
10
2020
pubmed:
7
10
2020
medline:
23
10
2020
Statut:
epublish
Résumé
We postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explore mesoderm lineage-bias within the human pluripotent stem cell compartment. We identify a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programmes. Functionally these cells initiate stem cell cultures and exhibit mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we 'trap' and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of 'cross-antagonistic' signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine.
Identifiants
pubmed: 33020476
doi: 10.1038/s41467-020-18727-8
pii: 10.1038/s41467-020-18727-8
pmc: PMC7536399
doi:
Substances chimiques
Culture Media
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4989Subventions
Organisme : Medical Research Council
ID : MR/R015724/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L012537/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L012650/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12796
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N000838/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137973817
Pays : United Kingdom
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