Open Accessp27 Kip1 Constrains Proliferation of Neural Progenitor Cells in Adult Brain Under Homeostatic and Ischemic Conditions
Author(s) -
Qiu Jianhua,
Takagi Yasushi,
Harada Jun,
Topalkara Kamil,
Wang Yumei,
Sims John R.,
Zheng Guoguang,
Huang Paulina,
Ling Yun,
Scadden David T.,
Moskowitz Michael A.,
Cheng Tao
Publication year - 2009
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.1
Subject(s) - biology , subventricular zone , neural stem cell , progenitor cell , subgranular zone , stem cell , microbiology and biotechnology , neurogenesis , homeostasis , cyclin , haematopoiesis , hippocampal formation , neuroscience , ischemia , progenitor , cell cycle , immunology , medicine , cell , genetics
Abstract Cell cycle inhibition of neural stem and progenitor cells is critical for maintaining the stability of central nervous system in adults, but it may represent a significant hurdle for neural regeneration after injury. We have previously demonstrated that the cyclin‐dependent kinase inhibitor (CKI) p21 cip1/waf1 (p21) maintains the quiescence of neural stem‐like cells under cerebral ischemia, as similarly shown for the hematopoietic stem cells. Here, we report the distinct role of another CKI member, p27 kip1 (p27) in neural progenitor cells (NPCs) from adult brain (subventricular zone and hippocampal subgranular zone) under both homeostatic and ischemic conditions. The basal level of NPC proliferation in the p27−/− mice was higher than that in p27+/+ mice. Upon ischemia, the overall proliferation of NPCs continued to be higher in p27−/− mice than that in p27+/+ mice. Moreover, the increase of NPC proliferation in p27−/− mice remained until 2 weeks after ischemia, whereas it resumed back to the basal level in p27+/+ mice. As a result, newly generated neuronal cells in the granular layer of p27−/− brain were more abundant compared with p27+/+ controls. These new data demonstrate that p27 functions as a distinct inhibitor for NPC proliferation under homeostatic as well as ischemic conditions. S TEM CELLS 2009;27:920–927