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

Cell division history determines hematopoietic stem cell potency

View ORCID ProfileFumio Arai, View ORCID ProfilePatrick S Stumpf, Yoshiko M Ikushima, Kentaro Hosokawa, Aline Roch, Matthias P Lutolf, Toshio Suda, View ORCID ProfileBen D MacArthur
doi: https://doi.org/10.1101/503813
Fumio Arai
Kyushu University, 812-8582, Fukuoka, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Fumio Arai
Patrick S Stumpf
University of Southampton, Southampton, SO17 1BJ, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Patrick S Stumpf
Yoshiko M Ikushima
Research Institute National Center for Global Health and Medicine, 162-8655, Tokyo, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kentaro Hosokawa
Kyushu University, 812-8582, Fukuoka, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aline Roch
Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias P Lutolf
Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshio Suda
Cancer Science Institute, National University of Singapore, 14 Medical Drive, MD6, 117599 Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ben D MacArthur
University of Southampton, Southampton, SO17 1BJ, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ben D MacArthur
  • For correspondence: bdm@soton.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Loss of stem cell self-renewal may underpin aging. Here, we combined single cell profiling, deep-learning, mathematical modelling and in vivo functional studies to explore how hematopoietic stem cell (HSC) division patterns evolve with age. We trained an artificial neural network (ANN) to accurately identify cell types in the hematopoietic hierarchy and predict their age from their gene expression patterns. We then used this ANN to compare daughter cell identities immediately after HSC divisions, and found that HSC self-renewal declines sharply with age. Furthermore, while HSC cell divisions are deterministic and intrinsically-regulated in young and old age, they become stochastic and niche-sensitive in mid-life. Analysis of evolving division patterns indicated that the self-renewal ability an individual HSC depends upon number times it has divided previously. We propose a model of HSC proliferation that accurately predicts the accumulation of HSCs with age, and reconciles the stochastic and instructive views of fate commitment.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 15, 2019.
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 division history determines hematopoietic stem cell potency
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Cell division history determines hematopoietic stem cell potency
Fumio Arai, Patrick S Stumpf, Yoshiko M Ikushima, Kentaro Hosokawa, Aline Roch, Matthias P Lutolf, Toshio Suda, Ben D MacArthur
bioRxiv 503813; doi: https://doi.org/10.1101/503813
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Cell division history determines hematopoietic stem cell potency
Fumio Arai, Patrick S Stumpf, Yoshiko M Ikushima, Kentaro Hosokawa, Aline Roch, Matthias P Lutolf, Toshio Suda, Ben D MacArthur
bioRxiv 503813; doi: https://doi.org/10.1101/503813

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 (998)
  • Biochemistry (1489)
  • Bioengineering (943)
  • Bioinformatics (6821)
  • Biophysics (2418)
  • Cancer Biology (1784)
  • Cell Biology (2528)
  • Clinical Trials (106)
  • Developmental Biology (1692)
  • Ecology (2564)
  • Epidemiology (1493)
  • Evolutionary Biology (5018)
  • Genetics (3613)
  • Genomics (4625)
  • Immunology (1165)
  • Microbiology (4244)
  • Molecular Biology (1622)
  • Neuroscience (10780)
  • Paleontology (82)
  • Pathology (236)
  • Pharmacology and Toxicology (409)
  • Physiology (555)
  • Plant Biology (1455)
  • Scientific Communication and Education (411)
  • Synthetic Biology (542)
  • Systems Biology (1871)
  • Zoology (259)