UHRF1 Licensed Self-Renewal of Active Adult Neural Stem Cells

Stem Cells
Albert BlanchartPatrik Ernfors

Abstract

Adult neurogenesis in the brain continuously seeds new neurons throughout life, but how homeostasis of adult neural stem cells (NSCs) is maintained is incompletely understood. Here, we demonstrate that the DNA methylation adapter ubiquitin-like, containing PHD and RING finger domains-1 (UHRF1) is expressed in, and regulates proliferation of, the active but not quiescent pool of adult neural progenitor cells. Mice with a neural stem cell-specific deficiency in UHRF1 exhibit a massive depletion of neurogenesis resulting in a collapse of formation of new neurons. In the absence of UHRF1, NSCs unexpectedly remain in the cell cycle but with a 17-fold increased cell cycle length due to a failure of replication phase entry caused by promoter demethylation and derepression of Cdkn1a, which encodes the cyclin-dependent kinase inhibitor p21. UHRF1 does not affect the proportion progenitor cells active within the cell cycle but among these cells, UHRF1 is critical for licensing replication re-entry. Therefore, this study shows that a UHRF1-Cdkn1a axis is essential for the control of stem cell self-renewal and neurogenesis in the adult brain. Stem Cells 2018;36:1736-1751.

References

Apr 1, 1992·Genetic Analysis, Techniques and Applications·T H BestorH Prydz
Feb 16, 1996·Science·C LoisA Alvarez-Buylla
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·F Doetsch, A Alvarez-Buylla
Jan 9, 1999·Mammalian Genome : Official Journal of the International Mammalian Genome Society·A FujimoriM Muto
Apr 15, 2000·Cell Research·D Donjerkovic, D W Scott
Apr 3, 2001·Nature Reviews. Neuroscience·A Alvarez-BuyllaA D Tramontin
Jan 10, 2002·Genes & Development·Adrian Bird
Aug 3, 2002·Oncogene·Peter A Jones
Dec 24, 2004·The EMBO Journal·Carmen BrennerFrançois Fuks
Aug 10, 2005·Archives of Neurology·Shazia K AfridiPeter J Goadsby
Dec 13, 2005·Nature Clinical Practice. Oncology·Stephen B Baylin
Dec 22, 2006·Molecular Biology of the Cell·Roberto PapaitIan Marc Bonapace
May 4, 2007·Current Opinion in Neurobiology·Jovica Ninkovic, Magdalena Götz
Aug 4, 2007·Science·Magnolia BostickSteven E Jacobsen
Jan 19, 2008·Nature Reviews. Genetics·Keith W Orford, David T Scadden
Feb 13, 2008·Developmental Cell·Arnaud BessonJames M Roberts
Feb 26, 2008·Cell·Chunmei ZhaoFred H Gage
Sep 6, 2008·Nature·Hideharu HashimotoXiaodong Cheng
Nov 27, 2008·Bioinformatics·Seth CarbonUNKNOWN Web Presence Working Group
Dec 6, 2008·Nucleic Acids Research·Jong Kyong KimSriharsa Pradhan
Apr 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Erika PastranaFiona Doetsch
Nov 11, 2009·International Review of Neurobiology·Jian Feng, Guoping Fan
Dec 25, 2009·Nature·Maria Stella CarroAntonio Iavarone
May 18, 2010·Current Opinion in Neurobiology·Yangling MuFred H Gage
Dec 4, 2010·Developmental Biology·Rachel K TittleJeffrey M Gross
May 21, 2011·Journal of Cellular Biochemistry·Garwin PichlerHeinrich Leonhardt
Oct 2, 2012·Nature Structural & Molecular Biology·Scott B RothbartBrian D Strahl
Nov 30, 2012·Annual Review of Physiology·Gabriel LepousezPierre-Marie Lledo
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Giovanna PontiArturo Alvarez-Buylla

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Citations

May 3, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yiwen ZhangHui Zhang
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Pedro VizánSergi Aranda
Aug 17, 2021·Stem Cells·Claudia Colussi, Claudio Grassi

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