Cell size is a determinant of stem cell potential during aging

Jette Lengefeld; Chia Wei Cheng; Pema Maretich; Marguerite Blair; Hannah Hagen; Melanie R. McReynolds; Emily Sullivan; Kyra Majors; Christina Roberts; Joon Ho Kang; Joachim D. Steiner; Teemu P. Miettinen; Scott R. Manalis; Adam Antebi; Sean J. Morrison; Jacqueline A. Lees; Laurie A. Boyer; Ömer H. Yilmaz; Angelika Amon

doi:10.1126/sciadv.abk0271

Cell size is a determinant of stem cell potential during aging

Jette Lengefeld, Chia Wei Cheng, Pema Maretich, Marguerite Blair, Hannah Hagen, Melanie R. McReynolds, Emily Sullivan, Kyra Majors, Christina Roberts, Joon Ho Kang, Joachim D. Steiner, Teemu P. Miettinen, Scott R. Manalis, Adam Antebi, Sean J. Morrison, Jacqueline A. Lees, Laurie A. Boyer, Ömer H. Yilmaz, Angelika Amon

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61 Scopus citations

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.

Original language	English (US)
Article number	eabk0271
Journal	Science Advances
Volume	7
Issue number	46
DOIs	https://doi.org/10.1126/sciadv.abk0271
State	Published - Nov 2021

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Lengefeld, J., Cheng, C. W., Maretich, P., Blair, M., Hagen, H., McReynolds, M. R., Sullivan, E., Majors, K., Roberts, C., Kang, J. H., Steiner, J. D., Miettinen, T. P., Manalis, S. R., Antebi, A., Morrison, S. J., Lees, J. A., Boyer, L. A., Yilmaz, Ö. H., & Amon, A. (2021). Cell size is a determinant of stem cell potential during aging. Science Advances, 7(46), Article eabk0271. https://doi.org/10.1126/sciadv.abk0271

Lengefeld, J, Cheng, CW, Maretich, P, Blair, M, Hagen, H, McReynolds, MR, Sullivan, E, Majors, K, Roberts, C, Kang, JH, Steiner, JD, Miettinen, TP, Manalis, SR, Antebi, A, Morrison, SJ, Lees, JA, Boyer, LA, Yilmaz, ÖH & Amon, A 2021, 'Cell size is a determinant of stem cell potential during aging', Science Advances, vol. 7, no. 46, eabk0271. https://doi.org/10.1126/sciadv.abk0271

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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 = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors.",

year = "2021",

month = nov,

doi = "10.1126/sciadv.abk0271",

language = "English (US)",

volume = "7",

journal = "Science Advances",

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AU - Lengefeld, Jette

AU - Cheng, Chia Wei

AU - Maretich, Pema

AU - Blair, Marguerite

AU - Hagen, Hannah

AU - McReynolds, Melanie R.

AU - Sullivan, Emily

AU - Majors, Kyra

AU - Roberts, Christina

AU - Kang, Joon Ho

AU - Steiner, Joachim D.

AU - Miettinen, Teemu P.

AU - Manalis, Scott R.

AU - Antebi, Adam

AU - Morrison, Sean J.

AU - Lees, Jacqueline A.

AU - Boyer, Laurie A.

AU - Yilmaz, Ömer H.

AU - Amon, Angelika

PY - 2021/11

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AB - 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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Cell size is a determinant of stem cell potential during aging

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