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

Authors
  • Rydström, Anna1
  • Mansell, Els2
  • Sigurdsson, Valgardur1
  • Sjöberg, Julia1
  • Soneji, Shamit3
  • Miharada, Kenichi4
  • Larsson, Jonas5
  • 1 Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden. , (Sweden)
  • 2 Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden; Stem Cell Group, Cancer Institute, University College London, London, UK. , (Sweden)
  • 3 Division of Molecular Hematology, Lund Stem Cell Center, Lund University, Lund, Sweden. , (Sweden)
  • 4 International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan. , (Japan)
  • 5 Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden. Electronic address: [email protected]. , (Sweden)
Type
Published Article
Journal
Stem Cell Reports
Publisher
Elsevier
Publication Date
Mar 14, 2023
Volume
18
Issue
3
Pages
736–748
Identifiers
DOI: 10.1016/j.stemcr.2023.01.014
PMID: 36868231
Source
Medline
Keywords
Language
English
License
Unknown

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. 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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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