Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain

被引：282

作者：

Kalamakis, Georgios ^{[1
,2
]}

Bruene, Daniel ^{[1
]}

Ravichandran, Srikanth ^{[3
]}

Bolz, Jan ^{[1
]}

Fan, Wenqiang ^{[7
,8
]}

Ziebell, Frederik ^{[1
,11
]}

Stiehl, Thomas ^{[11
]}

Catala-Martinez, Francisco ^{[1
]}

Kupke, Janina ^{[1
]}

Zhao, Sheng ^{[1
]}

Llorens-Bobadilla, Enric ^{[1
]}

Bauer, Katharina ^{[12
]}

Limpert, Stefanie ^{[1
]}

Berger, Birgit ^{[1
]}

Christen, Urs ^{[13
]}

Schmezer, Peter ^{[14
]}

Mallm, Jan Philipp ^{[15
,16
]}

Berninger, Benedikt ^{[7
,8
,9
,10
]}

Anders, Simon ^{[17
]}

del Sol, Antonio ^{[3
,4
,5
,6
]}

Marciniak-Czochra, Anna ^{[11
]}

Martin-Villalba, Ana ^{[1
]}

机构：

[1] German Canc Res Ctr, Mol Neurobiol, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, D-69120 Heidelberg, Germany

[3] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Luxembourg, Luxembourg

[4] CIC BioGUNE, Derio 48160, Spain

[5] Basque Fdn Sci, IKERBASQUE, Bilbao 48009, Spain

[6] Moscow Inst Phys & Technol, Dolgoprudnyi 141700, Russia

[7] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Physiol Chem, D-55128 Mainz, Germany

[8] Johannes Gutenberg Univ Mainz, Focus Program Translat Neurosci, D-55131 Mainz, Germany

[9] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Dev Neurobiol, London SE1 1UL, England

[10] Kings Coll London, MRC, Ctr Neurodev Disorders, Inst Psychiat Psychol & Neurosci, London SE1 1UL, England

[11] Heidelberg Univ, Interdisciplinary Ctr Sci Comp & Bioquant, Inst Appl Math, D-69120 Heidelberg, Germany

[12] German Canc Res Ctr, Heidelberg Ctr Personalized Oncol DKFZ HIPO, D-69120 Heidelberg, Germany

[13] Goethe Univ Hosp Frankfurt ZAFES, D-60596 Frankfurt, Germany

[14] German Canc Res Ctr, Div Epigen & Canc Risk Factors, D-69120 Heidelberg, Germany

[15] German Canc Res Ctr, Div Chromatin Networks, D-69120 Heidelberg, Germany

[16] German Canc Res Ctr, Single Cell Open Lab, D-69120 Heidelberg, Germany

[17] Heidelberg Univ, Ctr Mol Biol, D-69120 Heidelberg, Germany

来源：

CELL | 2019年 / 176卷 / 06期

关键词：

NEURAL STEM; RNA-SEQ; TRANSCRIPTOMICS REVEALS; SUBVENTRICULAR ZONE; ADULT NEUROGENESIS; SYSTEMS BIOLOGY; EPENDYMAL CELLS; SELF-RENEWAL; AGE; WNT;

D O I：

10.1016/j.cell.2019.01.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The function of somatic stem cells declines with age. Understanding the molecular underpinnings of this decline is key to counteract age-related disease. Here, we report a dramatic drop in the neural stem cells (NSCs) number in the aging murine brain. We find that this smaller stem cell reservoir is protected from full depletion by an increase in quiescence that makes old NSCs more resistant to regenerate the injured brain. Once activated, however, young and old NSCs show similar proliferation and differentiation capacity. Single-cell transcriptomics of NSCs indicate that aging changes NSCs minimally. In the aging brain, niche-derived inflammatory signals and the Wnt antagonist sFRP5 induce quiescence. Indeed, intervention to neutralize them increases activation of old NSCs during homeostasis and following injury. Our study identifies quiescence as a key feature of old NSCs imposed by the niche and uncovers ways to activate NSCs to repair the aging brain.

引用

页码：1407 / +

页数：27

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