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MAC-1 marks a quiescent and functionally superior HSC subset during regeneration

Rydström, Anna LU ; Mansell, Els LU ; Sigurdsson, Valgardur LU ; Sjöberg, Julia LU ; Soneji, Shamit LU ; Miharada, Kenichi LU and Larsson, Jonas LU (2023) In Stem Cell Reports 18(3). p.736-748
Abstract

Mouse hematopoietic stem cells (HSCs) have been extensively defined both molecularly and functionally at steady state, while regenerative stress induces immunophenotypical changes that limit high purity isolation and analysis. It is therefore important to identify markers that specifically label activated HSCs to gain further knowledge about their molecular and functional properties. Here, we assessed the expression of macrophage-1 antigen (MAC-1) on HSCs during regeneration following transplantation and observed a transient increase in MAC-1 expression during the early reconstitution phase. Serial transplantation experiments demonstrated that reconstitution potential was highly enriched in the MAC-1+ portion of the HSC pool.... (More)

Mouse hematopoietic stem cells (HSCs) have been extensively defined both molecularly and functionally at steady state, while regenerative stress induces immunophenotypical changes that limit high purity isolation and analysis. It is therefore important to identify markers that specifically label activated HSCs to gain further knowledge about their molecular and functional properties. Here, we assessed the expression of macrophage-1 antigen (MAC-1) on HSCs during regeneration following transplantation and observed a transient increase in MAC-1 expression during the early reconstitution phase. Serial transplantation experiments demonstrated that reconstitution potential was highly enriched in the MAC-1+ portion of the HSC pool. Moreover, in contrast to previous reports, we found that MAC-1 expression inversely correlates with cell cycling, and global transcriptome analysis showed that regenerating MAC-1+ HSCs share molecular features with stem cells with low mitotic history. Taken together, our results suggest that MAC-1 expression marks predominantly quiescent and functionally superior HSCs during early regeneration.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hematopoietic stem cells, MAC-1, regeneration, transplantation
in
Stem Cell Reports
volume
18
issue
3
pages
13 pages
publisher
Cell Press
external identifiers
  • scopus:85150366856
  • pmid:36868231
ISSN
2213-6711
DOI
10.1016/j.stemcr.2023.01.014
language
English
LU publication?
yes
id
fea22957-b5d5-4b48-a677-10182e1b8d51
date added to LUP
2023-05-05 08:27:22
date last changed
2024-06-15 02:39:39
@article{fea22957-b5d5-4b48-a677-10182e1b8d51,
  abstract     = {{<p>Mouse hematopoietic stem cells (HSCs) have been extensively defined both molecularly and functionally at steady state, while regenerative stress induces immunophenotypical changes that limit high purity isolation and analysis. It is therefore important to identify markers that specifically label activated HSCs to gain further knowledge about their molecular and functional properties. Here, we assessed the expression of macrophage-1 antigen (MAC-1) on HSCs during regeneration following transplantation and observed a transient increase in MAC-1 expression during the early reconstitution phase. Serial transplantation experiments demonstrated that reconstitution potential was highly enriched in the MAC-1<sup>+</sup> portion of the HSC pool. Moreover, in contrast to previous reports, we found that MAC-1 expression inversely correlates with cell cycling, and global transcriptome analysis showed that regenerating MAC-1<sup>+</sup> HSCs share molecular features with stem cells with low mitotic history. Taken together, our results suggest that MAC-1 expression marks predominantly quiescent and functionally superior HSCs during early regeneration.</p>}},
  author       = {{Rydström, Anna and Mansell, Els and Sigurdsson, Valgardur and Sjöberg, Julia and Soneji, Shamit and Miharada, Kenichi and Larsson, Jonas}},
  issn         = {{2213-6711}},
  keywords     = {{hematopoietic stem cells; MAC-1; regeneration; transplantation}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{736--748}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{MAC-1 marks a quiescent and functionally superior HSC subset during regeneration}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2023.01.014}},
  doi          = {{10.1016/j.stemcr.2023.01.014}},
  volume       = {{18}},
  year         = {{2023}},
}