Troy plus brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy

被引：130

作者：

Basak, Onur ^{[1
,2
,3
,9
,10
]}

Krieger, Teresa G. ^{[4
]}

Muraro, Mauro J. ^{[1
,2
,3
]}

Wiebrands, Kay ^{[1
,2
,3
]}

Stange, Daniel E. ^{[1
,2
,3
,11
]}

Frias-Aldeguer, Javier ^{[1
,2
,5
]}

Rivron, Nicolas C. ^{[1
,2
,5
]}

van de Wetering, Marc ^{[1
,2
,3
,6
]}

van Es, Johan H. ^{[1
,2
,3
]}

van Oudenaarden, Alexander ^{[1
,2
,3
]}

Simons, Benjamin D. ^{[4
,7
,8
]}

Clevers, Hans ^{[1
,2
,3
,6
]}

机构：

[1] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Canc Genom Netherlands, NL-3584 GC Utrecht, Netherlands

[4] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England

[5] Maastricht Univ, MERLN Inst Technol Inspired Regenerat Med, NL-6229 ER Maastricht, Netherlands

[6] Princess Maxima Ctr, NL-3584 CT Utrecht, Netherlands

[7] Univ Cambridge, Dept Phys, Cavendish Lab, Cambridge CB3 0HE, England

[8] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1TN, England

[9] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands

[10] Univ Utrecht, NL-3584 CG Utrecht, Netherlands

[11] Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, Univ Hosp Carl Gustav Carus, D-01069 Dresden, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 04期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

neural stem cells; cellular dynamics; modeling; single; cell sequencing; ki67; ADULT SUBVENTRICULAR ZONE; SELF-RENEWAL; VASCULAR NICHE; LINEAGE PROGRESSION; SUBEPENDYMAL ZONE; SONIC HEDGEHOG; NEUROGENESIS; REVEALS; SIGNALS; PROTEIN;

D O I：

10.1073/pnas.1715911114

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67(iresCreER) allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.

引用

页码：E610 / E619

页数：10

共 69 条

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