Open AccessUHRF1 Licensed Self‐Renewal of Active Adult Neural Stem Cells
Author(s) -
Blanchart Albert,
Navis Anna C.,
AssaifeLopes Natalia,
Usoskin Dmitry,
Aranda Sergi,
Sontheimer Jana,
Ernfors Patrik
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2889
Subject(s) - biology , neurogenesis , neural stem cell , microbiology and biotechnology , progenitor cell , cell cycle , stem cell , adult stem cell , cellular differentiation , cell , genetics , gene
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