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Continuous mitotic activity of primitive hematopoietic stem cells in adult mice

Morcos, Mina N.F. ; Zerjatke, Thomas ; Glauche, Ingmar ; Munz, Clara M. ; Ge, Yan ; Petzold, Andreas ; Reinhardt, Susanne ; Dahl, Andreas ; Anstee, Natasha S. and Bogeska, Ruzhica , et al. (2020) In Journal of Experimental Medicine 217(6).
Abstract

The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division–independent half-lives of H2B-FPs to be... (More)

The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division–independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
217
issue
6
article number
e20191284
publisher
Rockefeller University Press
external identifiers
  • scopus:85086649899
  • pmid:32302400
ISSN
0022-1007
DOI
10.1084/jem.20191284
language
English
LU publication?
yes
id
87dd476f-c8f9-4524-a38e-5ec0e10477a1
date added to LUP
2020-12-29 15:14:03
date last changed
2024-05-30 02:12:56
@article{87dd476f-c8f9-4524-a38e-5ec0e10477a1,
  abstract     = {{<p>The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division–independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.</p>}},
  author       = {{Morcos, Mina N.F. and Zerjatke, Thomas and Glauche, Ingmar and Munz, Clara M. and Ge, Yan and Petzold, Andreas and Reinhardt, Susanne and Dahl, Andreas and Anstee, Natasha S. and Bogeska, Ruzhica and Milsom, Michael D. and Säwén, Petter and Wan, Haixia and Bryder, David and Roers, Axel and Gerbaulet, Alexander}},
  issn         = {{0022-1007}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{Continuous mitotic activity of primitive hematopoietic stem cells in adult mice}},
  url          = {{http://dx.doi.org/10.1084/jem.20191284}},
  doi          = {{10.1084/jem.20191284}},
  volume       = {{217}},
  year         = {{2020}},
}