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

Nature Communications
Daniel W HageyJonas Muhr

Abstract

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.

References

Oct 11, 1991·Science·S K McConnell, C E Kaznowski
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Jun 8, 2002·Annual Review of Neuroscience·Nicholas Gaiano, Gord Fishell
Oct 1, 2003·Nature Neuroscience·Magdalena BylundJonas Muhr
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Oct 26, 2005·Current Opinion in Cell Biology·Wieland B Huttner, Yoichi Kosodo
Nov 30, 2005·Nature Reviews. Molecular Cell Biology·Magdalena Götz, Wieland B Huttner
May 22, 2007·Nature Reviews. Neuroscience·Bradley J MolyneauxJeffrey D Macklis
Jan 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Martin Rosvall, Carl T Bergstrom
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Jan 10, 2008·Annual Review of Cell and Developmental Biology·Shahragim TajbakhshIsabelle Le Roux
Dec 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Louis-Jan PilazColette Dehay
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Juergen A Knoblich
Jan 13, 2011·Nature Communications·Yoko AraiWieland B Huttner
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Agnès I Lukaszewicz, David J Anderson
Aug 2, 2011·Annual Review of Cell and Developmental Biology·Maria K Lehtinen, Christopher A Walsh
May 5, 2012·Current Opinion in Neurobiology·Madeline A Lancaster, Juergen A Knoblich
Aug 11, 2012·Science·Santos J FrancoUlrich Müller
Apr 11, 2013·Development·Michelle S Lu, Christopher A Johnston
Sep 24, 2013·Nature Methods·Simone PicelliRickard Sandberg
Oct 1, 2013·Cell·Siim Pauklin, Ludovic Vallier
May 20, 2014·Nature Methods·Peter V KharchenkoDavid T Scadden
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
May 23, 2015·Neuron·Cristina Gil-SanzUlrich Müller
Aug 2, 2015·Cell·Kevin Andrew Uy GonzalesHuck-Hui Ng
Apr 21, 2016·Nature Communications·Mayumi OkamotoAyano Kawaguchi
Jul 9, 2017·Cancer Research·Idha KurtsdotterJonas Muhr

❮ Previous
Next ❯

Citations

May 2, 2021·Journal of Experimental & Clinical Cancer Research : CR·Xiaoqing SunHuanxin Lin
May 20, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jonas Muhr, Daniel W Hagey
May 30, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Ylva Engström
Jun 5, 2021·Seminars in Cell & Developmental Biology·Belal ShohayebHelen M Cooper

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
FACS
Drop-seq
dissection
PCA
flow cytometry
PCR

Software Mentioned

FACSDiVa
R package hclust
Smartseq2
BD
ImageJ
Monocle
Monocle DDRTree
WGCNA
Infomap
R

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.