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

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age

Mati Mann, Arnav Mehta, Carl de Boer, Monika S. Kowalczyk, Kevin Lee, Noga Rogel, Abigail R. Knecht, Daneyal Farouq, Aviv Regev, David Baltimore
doi: https://doi.org/10.1101/163402
Mati Mann
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arnav Mehta
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
2David Geffen School of Medicine, UCLA, Los Angeles, CA 90025, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carl de Boer
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monika S. Kowalczyk
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Lee
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noga Rogel
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abigail R. Knecht
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daneyal Farouq
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aviv Regev
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
4Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Biology, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: baltimo@caltech.edu aregev@broadinstitute.org
David Baltimore
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: baltimo@caltech.edu aregev@broadinstitute.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. With age, however, they produce a myeloid-biased output that may lead to poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Using single-cell RNA-seq, we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is much more common amongst aged LT-HSCs and is uniquely primed to respond to acute inflammatory challenge. We predict several transcription factors to regulate differentially expressed genes between mLT-HSCs and other LT-HSC subsets. Among these, we show that Klf5, Ikzf1 and Stat3 play important roles in age-related inflammatory myeloid bias. These factors may regulate myeloid versus lymphoid balance with age, and can potentially mitigate the long-term deleterious effects of inflammation that lead to hematopoietic pathologies.

  • LT-HSCs from young and aged mice have differential responses to acute inflammatory challenge.

  • HSPCs directly sense inflammatory stimuli in vitro and have a robust transcriptional response.

  • Aged LT-HSCs demonstrate a cell-intrinsic myeloid bias during inflammatory challenge.

  • Single-cell RNA-seq unmasked the existence of two subsets within the LT-HSC population that was apparent upon stimulation but not steady-state. One of the LT-HSC subsets is more prevalent in young and the other in aged mice.

  • Klf5, Ikzf1 and Stat3 regulate age‐ and inflammation-related LT-HSC myeloid-bias.

One sentence summary Murine hematopoietic stem cells display transcriptional heterogeneity that is quantitatively altered with age and leads to the age-dependent myeloid bias evident after inflammatory challenge.

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-ND 4.0 International license.
Back to top
PreviousNext
Posted November 14, 2017.
Download PDF

Supplementary Material

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.
Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age
(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
Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age
Mati Mann, Arnav Mehta, Carl de Boer, Monika S. Kowalczyk, Kevin Lee, Noga Rogel, Abigail R. Knecht, Daneyal Farouq, Aviv Regev, David Baltimore
bioRxiv 163402; doi: https://doi.org/10.1101/163402
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age
Mati Mann, Arnav Mehta, Carl de Boer, Monika S. Kowalczyk, Kevin Lee, Noga Rogel, Abigail R. Knecht, Daneyal Farouq, Aviv Regev, David Baltimore
bioRxiv 163402; doi: https://doi.org/10.1101/163402

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

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4861)
  • Biochemistry (10811)
  • Bioengineering (8054)
  • Bioinformatics (27346)
  • Biophysics (13999)
  • Cancer Biology (11140)
  • Cell Biology (16087)
  • Clinical Trials (138)
  • Developmental Biology (8793)
  • Ecology (13307)
  • Epidemiology (2067)
  • Evolutionary Biology (17375)
  • Genetics (11694)
  • Genomics (15939)
  • Immunology (11042)
  • Microbiology (26132)
  • Molecular Biology (10669)
  • Neuroscience (56660)
  • Paleontology (420)
  • Pathology (1737)
  • Pharmacology and Toxicology (3009)
  • Physiology (4557)
  • Plant Biology (9648)
  • Scientific Communication and Education (1617)
  • Synthetic Biology (2695)
  • Systems Biology (6985)
  • Zoology (1511)