Prospective Identification and Purification of Quiescent Adult Neural Stem Cells from Their In Vivo Niche

被引：461

作者：

Codega, Paolo ^{[1
,6
]}

Silva-Vargas, Violeta ^{[1
,6
]}

Paul, Alex ^{[4
,6
]}

Maldonado-Soto, Angel R. ^{[3
,6
]}

DeLeo, Annina M. ^{[1
,6
]}

Pastrana, Erika ^{[1
]}

Doetsch, Fiona ^{[1
,2
,3
,5
,6
,7
,8
]}

机构：

[1] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[2] Columbia Univ, Dept Neurol, New York, NY 10032 USA

[3] Columbia Univ, Dept Neurosci, New York, NY 10032 USA

[4] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[5] Columbia Univ, Dept Rehabil & Regenerat Med, New York, NY 10032 USA

[6] Columbia Univ, Columbia Stem Cell Initiat, New York, NY 10032 USA

[7] Columbia Univ, Motor Neuron Ctr, New York, NY 10032 USA

[8] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

来源：

NEURON | 2014年 / 82卷 / 03期

关键词：

SUBVENTRICULAR ZONE; PROGENITOR PROLIFERATION; SUBEPENDYMAL ZONE; VASCULAR NICHE; LINEAGE CELLS; SELF-RENEWAL; HUMAN BRAIN; EXPRESSION; ACTIVATION; FOREBRAIN;

D O I：

10.1016/j.neuron.2014.02.039

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Adult neurogenic niches harbor quiescent neural stem cells; however, their in vivo identity has been elusive. Here, we prospectively isolate GFAP(+)CD133(+) (quiescent neural stem cells [qNSCs]) and GFAP(+)CD133(+) EGFR(+) (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro. In contrast, qNSCs are largely dormant in vivo, generate olfactory bulb interneurons with slower kinetics, and only rarely form colonies in vitro. Moreover, qNSCs are Nestin negative, a marker widely used for neural stem cells. Upon activation, qNSCs upregulate Nestin and EGFR and become highly proliferative. Notably, qNSCs and aNSCs can interconvert in vitro. Transcriptome analysis reveals that qNSCs share features with quiescent stem cells from other organs. Finally, small-molecule screening identified the GPCR ligands, S1P and PGD2, as factors that actively maintain the quiescent state of qNSCs.

引用

页码：545 / 559

页数：15

共 81 条

[1] In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog [J].