Cell size is a determinant of stem cell potential during aging
J. Lengefeld, C.-W. Cheng, P. Maretich, M. R. McReynolds, M. Blair, H. Hagen, E. J. Sullivan, K. Majors, C. Roberts, J. H. Kang, J. Steiner, T. P. Miettinen, S. Manalis, A. Antebi, S. J. Morrison, J. Lees, L. Boyer, O. H. Yilmaz, A. Amon
Abstract
Stem cells are remarkably small in size. Whether small size is important for stem cell function is unknown. We find that murine hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. Preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing large HSCs size by shortening G1 averts the loss of stem cell potential under conditions causing stem cell exhaustion. Finally, we show that a fraction of 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. One Sentence SummarySize increase drives stem cell aging.
02 /Specification & Classification
Click any tag to browse matching papersReproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice
Yuting Wang, Wenhao Zhang, … Yi Zhang·Cell ResearchPeer-reviewed·Jan 2, 2025
- An aged human bone marrow mesenchymal niche causes impaired function of human hematopoietic stem cells under regeneration-induced stress
Ani Grigoryan, Ruba Abdelrahman, … Paul Emile Bourgine·bioRxiv·Oct 28, 2026
- Megakaryocyte Progenitor Cell Function is Enhanced Upon Aging Despite the Functional Decline of Aged Hematopoietic Stem Cells
D. Poscablo, A. Worthington, … C. Forsberg·Stem Cell ReportsPeer-reviewed·Jun 1, 2021
- Hematopoietic Stem and Progenitor Cell Aging is Initiated at Middle Age Through Decline in Local Insulin-Like Growth Factor 1 (IGF1)
Kira Young, Elizabeth Eudy, … Jennifer Trowbridge·bioRxiv·Jul 11, 2020
- Proliferative events ameliorate DNA damage accumulation without affecting function in hematopoietic stem cells
Shubham Haribhau Mehatre, Harsh Agrawal, … Satish Khurana·Life Science AlliancePeer-reviewed·Jan 21, 2026
- Heme oxygenase-1 deficiency affects bone marrow niche and triggers premature exhaustion of hematopoietic stem cells.
K. Szade, M. Zukowska, … A. Jozkowicz·bioRxiv·Dec 10, 2018