CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment.
Animals
CDC2 Protein Kinase
/ physiology
Cell Cycle
Cell Differentiation
Cell Lineage
Cell Separation
Cerebral Cortex
/ embryology
Cyclin B1
/ physiology
Cyclin B2
/ physiology
Cyclin D1
/ physiology
Female
Flow Cytometry
Gene Expression Regulation, Developmental
Mice
Mice, Inbred C57BL
Neuroglia
/ metabolism
Sequence Analysis, RNA
Signal Transduction
Stem Cells
/ cytology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
20
08
2019
accepted:
13
05
2020
entrez:
11
6
2020
pubmed:
11
6
2020
medline:
28
8
2020
Statut:
epublish
Résumé
The sequential generation of layer-specific cortical neurons requires radial glia cells (RGCs) to precisely balance self-renewal and lineage commitment. While specific cell-cycle phases have been associated with these decisions, the mechanisms linking the cell-cycle machinery to cell-fate commitment remain obscure. Using single-cell RNA-sequencing, we find that the strongest transcriptional signature defining multipotent RGCs is that of G2/M-phase, and particularly CYCLIN-B1/2, while lineage-committed progenitors are enriched in G1/S-phase genes, including CYCLIN-D1. These data also reveal cell-surface markers that allow us to isolate RGCs and lineage-committed progenitors, and functionally confirm the relationship between cell-cycle phase enrichment and cell fate competence. Finally, we use cortical electroporation to demonstrate that CYCLIN-B1/2 cooperate with CDK1 to maintain uncommitted RGCs by activating the NOTCH pathway, and that CYCLIN-D1 promotes differentiation. Thus, this work establishes that cell-cycle phase-specific regulators act in opposition to coordinate the self-renewal and lineage commitment of RGCs via core stem cell regulatory pathways.
Identifiants
pubmed: 32518258
doi: 10.1038/s41467-020-16597-8
pii: 10.1038/s41467-020-16597-8
pmc: PMC7283355
doi:
Substances chimiques
Ccnb1 protein, mouse
0
Ccnb2 protein, mouse
0
Ccnd1 protein, mouse
0
Cyclin B1
0
Cyclin B2
0
Cyclin D1
136601-57-5
CDC2 Protein Kinase
EC 2.7.11.22
Cdk1 protein, mouse
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2898Références
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