Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice

被引:178
作者
Ponti, Giovanna [1 ,2 ,3 ,4 ]
Obernier, Kirsten [1 ,2 ]
Guinto, Cristina [1 ,2 ]
Jose, Lingu [1 ,2 ]
Bonfanti, Luca [3 ,4 ]
Alvarez-Buylla, Arturo [1 ,2 ]
机构
[1] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
[3] Univ Turin, Dept Vet Sci, I-10043 Turin, Italy
[4] Univ Turin, Neurosci Inst Cavalieri Ottolenghi, I-10043 Turin, Italy
基金
美国国家卫生研究院;
关键词
adult neurogenesis; circadian rhythm; subependymal; thymidine analogs toxicity; transit amplifying progenitors; STEM-CELLS; NEURONAL MIGRATION; SUBEPENDYMAL LAYER; DEPENDENT KINASES; S-PHASE; NEUROGENESIS; PROLIFERATION; BRAIN; MOUSE; RAT;
D O I
10.1073/pnas.1219563110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proliferating neural stem cells and intermediate progenitors persist in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain. This extensive germinal layer in the walls of the lateral ventricles is the site of birth of different types of interneurons destined for the olfactory bulb. The cell cycle dynamics of stem cells (B1 cells), intermediate progenitors (C cells), and neuroblasts (A cells) in the V-SVZ and the number of times these cells divide remain unknown. Using whole mounts of the walls of the lateral ventricles of adult mice and three cell cycle analysis methods using thymidine analogs, we determined the proliferation dynamics of B1, C, and A cells in vivo. Achaete-scute complex homolog (Ascl)1(+) C cells were heterogeneous with a cell cycle length (T-c) of 18-25 h and a long S phase length (T-s) of 14-17 h. After C cells, Double-cortin(+) A cells were the second-most common dividing cell type in the V-SVZ and had a T-c of 18 h and T-s of 9 h. Human glial fibrillary acidic protein (hGFAP)::GFP(+) B1 cells had a surprisingly short T-c of 17-18 h and a T-s of 4 h. Progenitor population analysis suggests that following the initial division of B1 cells, C cells divide three times and A cells once, possibly twice. These data provide essential information on the dynamics of adult progenitor cell proliferation in the V-SVZ and how large numbers of new neurons continue to be produced in the adult mammalian brain.
引用
收藏
页码:E1045 / E1054
页数:10
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