Cell size is a determinant of stem cell potential during aging

Jette Lengefeld(University of Helsinki), Chia‐Wei Cheng(Massachusetts Institute of Technology), Pema Maretich(Massachusetts Institute of Technology), Marguerite Blair(Massachusetts Institute of Technology), Hannah R. Hagen(Massachusetts Institute of Technology), Melanie R. McReynolds(Princeton University), Emily Sullivan(Massachusetts Institute of Technology), Kyra Majors(Massachusetts Institute of Technology), Christina Roberts(Max Planck Institute for Biology of Ageing), Joon Ho Kang(Massachusetts Institute of Technology), Joachim D. Steiner(University of Cologne), Teemu P. Miettinen(MRC Laboratory for Molecular Cell Biology), Scott R. Manalis(Massachusetts Institute of Technology), Adam Antebi(Max Planck Institute for Biology of Ageing), Sean J. Morrison(Howard Hughes Medical Institute), Jacqueline A. Lees(Massachusetts Institute of Technology), Laurie A. Boyer(Massachusetts Institute of Technology), Ömer Yılmaz(Massachusetts Institute of Technology), Angelika Amon(Howard Hughes Medical Institute)
Science Advances
November 12, 2021
10.1126/sciadv.abk0271
Cited by 164Open Access
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Abstract

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.

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