CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment.

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Hagey DW, Topcic D, Kee N, Reynaud F, Bergsland M, Perlmann T, Muhr J

Nat Commun 11 (1) 2898 [2020-06-09; online 2020-06-09]

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.

Bioinformatics Support for Computational Resources [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 32518258

DOI 10.1038/s41467-020-16597-8

Crossref 10.1038/s41467-020-16597-8

pii: 10.1038/s41467-020-16597-8
pmc: PMC7283355