Cell size is a determinant of stem cell potential during aging

被引：96

作者：

Lengefeld, Jette ^{[1
,2
]}

Cheng, Chia-Wei ^{[3
]}

Maretich, Pema ^{[4
]}

Blair, Marguerite ^{[3
]}

Hagen, Hannah ^{[3
]}

McReynolds, Melanie R. ^{[5
,6
]}

Sullivan, Emily ^{[3
]}

Majors, Kyra ^{[3
]}

Roberts, Christina ^{[7
,8
]}

Kang, Joon Ho ^{[3
,9
]}

Steiner, Joachim D. ^{[7
,8
,10
,11
]}

Miettinen, Teemu P. ^{[3
,12
]}

Manalis, Scott R. ^{[3
,13
,14
]}

Antebi, Adam ^{[7
,8
]}

Morrison, Sean J. ^{[15
,16
,17
]}

Lees, Jacqueline A. ^{[3
]}

Boyer, Laurie A. ^{[4
,13
]}

Yilmaz, Omer H. ^{[3
]}

Amon, Angelika ^{[1
,4
]}

机构：

[1] MIT, Howard Hughes Med Inst, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[2] Univ Helsinki, Inst Biotechnol, HiLIFE, Helsinki, Finland

[3] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] MIT, Dept Biol, Cambridge, MA USA

[5] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA

[6] Lewis Sigler Inst Integrat Genom, Princeton, NJ USA

[7] Univ Cologne, Max Planck Inst Biol Ageing, Cologne, Germany

[8] Univ Cologne, CECAD, Cologne, Germany

[9] MIT, Dept Phys, Cambridge, MA 02139 USA

[10] Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany

[11] Univ Hosp Cologne, Cologne, Germany

[12] UCL, MRC Lab Mol Cell Biol, London, England

[13] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[14] MIT, Dept Mech Engn, Cambridge, MA 02139 USA

[15] Univ Texas Southwestern Med Ctr Dallas, Childrens Res Inst, Dallas, TX 75390 USA

[16] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA

[17] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 46期

基金：

瑞士国家科学基金会; 芬兰科学院; 英国惠康基金;

关键词：

HEMATOPOIETIC STEM; SELF-RENEWAL; GENE-EXPRESSION; FUNCTIONAL DECLINE; PROGENITOR CELLS; GROWTH; SENESCENCE; CYCLE; HOMEOSTASIS; MTOR;

D O I：

10.1126/sciadv.abk0271

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：

Stem cells are remarkably small. Whether small size is important for stem cell function is unknown. We find that hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferation and was accompanied by altered metabolism. Preventing HSC enlargement or reducing large HSCs in size averts the loss of stem cell potential under conditions causing stem cell exhaustion. Last, we show that murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function in vivo and propose that stem cell enlargement contributes to their functional decline during aging.

引用

页数：16

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