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CD244 expression represents functional decline of murine hematopoietic stem cells after in vitro culture

Koide, Shuhei LU ; Sigurdsson, Valgardur LU ; Radulovic, Visnja LU ; Saito, Kiyoka LU ; Zheng, Zhiqian ; Lang, Stefan LU orcid ; Soneji, Shamit LU ; Iwama, Atsushi and Miharada, Kenichi LU (2022) In iScience 25(1).
Abstract

Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after in vitro culture. Here we show that cultured HSCs express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSCs were divided into CD244- and CD244+ subpopulations, and only CD244- cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the... (More)

Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after in vitro culture. Here we show that cultured HSCs express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSCs were divided into CD244- and CD244+ subpopulations, and only CD244- cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244+ subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244+ population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after in vitro culture thereby useful to elucidate mechanism of functional decline of HSCs during ex vivo treatment.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biological sciences, Cell biology, Immunology, Stem cells research
in
iScience
volume
25
issue
1
article number
103603
publisher
Elsevier
external identifiers
  • scopus:85121858666
  • pmid:35005548
ISSN
2589-0042
DOI
10.1016/j.isci.2021.103603
language
English
LU publication?
yes
id
b75c5039-42f2-4725-8108-b0d1840db4e6
date added to LUP
2022-10-14 15:18:12
date last changed
2024-06-13 20:11:01
@article{b75c5039-42f2-4725-8108-b0d1840db4e6,
  abstract     = {{<p>Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after in vitro culture. Here we show that cultured HSCs express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSCs were divided into CD244<sup>-</sup> and CD244<sup>+</sup> subpopulations, and only CD244<sup>-</sup> cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244<sup>+</sup> subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244<sup>+</sup> population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after in vitro culture thereby useful to elucidate mechanism of functional decline of HSCs during ex vivo treatment.</p>}},
  author       = {{Koide, Shuhei and Sigurdsson, Valgardur and Radulovic, Visnja and Saito, Kiyoka and Zheng, Zhiqian and Lang, Stefan and Soneji, Shamit and Iwama, Atsushi and Miharada, Kenichi}},
  issn         = {{2589-0042}},
  keywords     = {{Biological sciences; Cell biology; Immunology; Stem cells research}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{CD244 expression represents functional decline of murine hematopoietic stem cells after in vitro culture}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2021.103603}},
  doi          = {{10.1016/j.isci.2021.103603}},
  volume       = {{25}},
  year         = {{2022}},
}