Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Cell size is a determinant of stem cell potential during aging

View ORCID ProfileJette Lengefeld, Chia-Wei Cheng, View ORCID ProfilePema Maretich, Marguerite Blair, View ORCID ProfileHannah Hagen, View ORCID ProfileMelanie R. McReynolds, Emily Sullivan, Kyra Majors, Christina Roberts, Joon Ho Kang, View ORCID ProfileJoachim D. Steiner, View ORCID ProfileTeemu P. Miettinen, View ORCID ProfileScott R. Manalis, View ORCID ProfileAdam Antebi, Sean J. Morrison, View ORCID ProfileJacqueline A. Lees, View ORCID ProfileLaurie A. Boyer, Ömer H. Yilmaz, View ORCID ProfileAngelika Amon
doi: https://doi.org/10.1101/2020.10.27.355388
Jette Lengefeld
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jette Lengefeld
  • For correspondence: angelika@mit.edu ljette@mit.edu
Chia-Wei Cheng
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pema Maretich
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pema Maretich
Marguerite Blair
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hannah Hagen
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hannah Hagen
Melanie R. McReynolds
3Frick Laboratory, Department of Chemistry, Princeton, NJ, USA
4Lewis-Sigler Institute for Integrative Genomics, Princeton, NJ, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Melanie R. McReynolds
Emily Sullivan
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyra Majors
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christina Roberts
5Max Planck Institute for Biology of Ageing and CECAD, University of Cologne, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joon Ho Kang
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
6Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joachim D. Steiner
5Max Planck Institute for Biology of Ageing and CECAD, University of Cologne, Germany
7Department II of Internal Medicine and Center for Molecular Medicine, University of Cologne, Cologne, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joachim D. Steiner
Teemu P. Miettinen
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
8MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Teemu P. Miettinen
Scott R. Manalis
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
9Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
10Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott R. Manalis
Adam Antebi
5Max Planck Institute for Biology of Ageing and CECAD, University of Cologne, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Adam Antebi
Sean J. Morrison
11Children’s Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
12Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline A. Lees
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jacqueline A. Lees
Laurie A. Boyer
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
9Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Laurie A. Boyer
Ömer H. Yilmaz
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angelika Amon
1David H Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Angelika Amon
  • For correspondence: angelika@mit.edu ljette@mit.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

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 Summary Size increase drives stem cell aging.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 27, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Cell size is a determinant of stem cell potential during aging
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
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
bioRxiv 2020.10.27.355388; doi: https://doi.org/10.1101/2020.10.27.355388
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
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
bioRxiv 2020.10.27.355388; doi: https://doi.org/10.1101/2020.10.27.355388

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4118)
  • Biochemistry (8825)
  • Bioengineering (6529)
  • Bioinformatics (23481)
  • Biophysics (11800)
  • Cancer Biology (9221)
  • Cell Biology (13334)
  • Clinical Trials (138)
  • Developmental Biology (7442)
  • Ecology (11421)
  • Epidemiology (2066)
  • Evolutionary Biology (15169)
  • Genetics (10448)
  • Genomics (14054)
  • Immunology (9183)
  • Microbiology (22186)
  • Molecular Biology (8821)
  • Neuroscience (47614)
  • Paleontology (350)
  • Pathology (1430)
  • Pharmacology and Toxicology (2492)
  • Physiology (3736)
  • Plant Biology (8085)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2222)
  • Systems Biology (6042)
  • Zoology (1254)