@article{3b8ae41fd85c48e3a590ffcafe9f4b2a,
title = "Cell size is a determinant of stem cell potential during aging",
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.",
author = "Jette Lengefeld and Cheng, {Chia Wei} and Pema Maretich and Marguerite Blair and Hannah Hagen and McReynolds, {Melanie R.} and Emily Sullivan and Kyra Majors and Christina Roberts and Kang, {Joon Ho} and Steiner, {Joachim D.} and Miettinen, {Teemu P.} and Manalis, {Scott R.} and Adam Antebi and Morrison, {Sean J.} and Lees, {Jacqueline A.} and Boyer, {Laurie A.} and Yilmaz, {{\"O}mer H.} and Angelika Amon",
note = "Funding Information: J.L. was supported by the Howard Hughes Medical Institute (HHMI), Jane Coffin Childs Memorial Fund, Swiss National Science Foundation (SNSF), and the Academy of Finland. T.P.M. was supported by the Wellcome Trust (110275/Z/15/Z). This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD085866), NCI Cancer Centre core grant P30-CA14051 to the Ostrom Bioinformatics and Computing Core Facility of the Swanson Biotechnology Center, and the MIT Stem Cell Initiative through Fondation MIT. A.An. is also an investigator of the HHMI and the Glenn Foundation for Medical Research. P.M. and L.A.B. were supported by the Mathers Foundation, NIEHS P30-ES002109, and the G. Harold & Leila Y. Mathers Foundation. M.R.M. is supported by the Burroughs Wellcome Fund and HHMI via the PDEP and Hanna H. Gray Fellows Program. J.D.S. and A.An. were supported by ERC Advanced Grant: Nuage and the Max-Planck-Gesellschaft. M.R.M. was supported by the Gray Foundation. C.-W.C. was supported by NIH/R00 (DK123407). We are grateful to J. Saarikangas, J. Skotheim, G. Neurohr, X. Zhou, D. Corbi, S. Morrill, and the members of the Amon, Lees, and Yilmaz laboratories for discussions and for reading of the manuscript. We thank C. Whittaker, D. Pradhan, the Flow Cytometry Core, the KI Genomics Core/MIT BioMicro Centre, and the FACS & Imaging Core Facility at the Max Planck Institute for Biology of Ageing for analytical and technical support as well as P. H. Hsu, K. Knouse, and L. Zasadil for sharing material and protocols. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors.",
year = "2021",
month = nov,
doi = "10.1126/sciadv.abk0271",
language = "English (US)",
volume = "7",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "46",
}