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Continuous mitotic activity of primitive hematopoietic stem cells in adult mice

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 p...

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Autores principales: Morcos, Mina N.F., Zerjatke, Thomas, Glauche, Ingmar, Munz, Clara M., Ge, Yan, Petzold, Andreas, Reinhardt, Susanne, Dahl, Andreas, Anstee, Natasha S., Bogeska, Ruzhica, Milsom, Michael D., Säwén, Petter, Wan, Haixia, Bryder, David, Roers, Axel, Gerbaulet, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971128/
https://www.ncbi.nlm.nih.gov/pubmed/32302400
http://dx.doi.org/10.1084/jem.20191284
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author Morcos, Mina N.F.
Zerjatke, Thomas
Glauche, Ingmar
Munz, Clara M.
Ge, Yan
Petzold, Andreas
Reinhardt, Susanne
Dahl, Andreas
Anstee, Natasha S.
Bogeska, Ruzhica
Milsom, Michael D.
Säwén, Petter
Wan, Haixia
Bryder, David
Roers, Axel
Gerbaulet, Alexander
author_facet Morcos, Mina N.F.
Zerjatke, Thomas
Glauche, Ingmar
Munz, Clara M.
Ge, Yan
Petzold, Andreas
Reinhardt, Susanne
Dahl, Andreas
Anstee, Natasha S.
Bogeska, Ruzhica
Milsom, Michael D.
Säwén, Petter
Wan, Haixia
Bryder, David
Roers, Axel
Gerbaulet, Alexander
author_sort Morcos, Mina N.F.
collection PubMed
description 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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spelling pubmed-79711282021-03-26 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. Bogeska, Ruzhica Milsom, Michael D. Säwén, Petter Wan, Haixia Bryder, David Roers, Axel Gerbaulet, Alexander J Exp Med Article 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. Rockefeller University Press 2020-04-16 /pmc/articles/PMC7971128/ /pubmed/32302400 http://dx.doi.org/10.1084/jem.20191284 Text en © 2020 Morcos et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Morcos, Mina N.F.
Zerjatke, Thomas
Glauche, Ingmar
Munz, Clara M.
Ge, Yan
Petzold, Andreas
Reinhardt, Susanne
Dahl, Andreas
Anstee, Natasha S.
Bogeska, Ruzhica
Milsom, Michael D.
Säwén, Petter
Wan, Haixia
Bryder, David
Roers, Axel
Gerbaulet, Alexander
Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title_full Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title_fullStr Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title_full_unstemmed Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title_short Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
title_sort continuous mitotic activity of primitive hematopoietic stem cells in adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971128/
https://www.ncbi.nlm.nih.gov/pubmed/32302400
http://dx.doi.org/10.1084/jem.20191284
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