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

Sci Adv. 2021 Nov 12;7(46):eabk0271. doi: 10.1126/sciadv.abk0271. Epub 2021 Nov 12.

Authors

Jette Lengefeld^{1

2}, Chia-Wei Cheng³, Pema Maretich⁴, Marguerite Blair³, Hannah Hagen³, Melanie R McReynolds^{5

6}, Emily Sullivan³, Kyra Majors³, Christina Roberts⁷, Joon Ho Kang^{3

8}, Joachim D Steiner^{7

9}, Teemu P Miettinen^{3

10}, Scott R Manalis^{3

11

12}, Adam Antebi⁷, Sean J Morrison^{13

14}, Jacqueline A Lees³, Laurie A Boyer^{4

11}, Ömer H Yilmaz³, Angelika Amon^{1

4}

Affiliations

¹ David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
³ David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Chemistry, Princeton University, Princeton, NJ, USA.
⁶ Lewis-Sigler Institute for Integrative Genomics, Princeton, NJ, USA.
⁷ Max Planck Institute for Biology of Ageing and CECAD, University of Cologne, Cologne, Germany.
⁸ Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
¹⁰ MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
¹¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹² Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹³ Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁴ Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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.

Abstract

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