Cell size is a determinant of stem cell potential during aging

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...

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Published in:Science advances 2021-11, Vol.7 (46), p.eabk0271-eabk0271
Main Authors: Lengefeld, Jette, Cheng, Chia-Wei, Maretich, Pema, Blair, Marguerite, Hagen, Hannah, McReynolds, Melanie R, Sullivan, Emily, Majors, Kyra, Roberts, Christina, Kang, Joon Ho, Steiner, Joachim D, Miettinen, Teemu P, Manalis, Scott R, Antebi, Adam, Morrison, Sean J, Lees, Jacqueline A, Boyer, Laurie A, Yilmaz, Ömer H, Amon, Angelika
Format: Article
Language:English
Subjects:
Biomedicine and Life Sciences
Cell Biology
Health and Medicine
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Summary: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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abk0271