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Continuous mitotic activity of primitive hematopoietic stem cells in adult mice

Journal article
Authors M. N. F. Morcos
T. Zerjatke
I. Glauche
C. M. Munz
Y. Ge
A. Petzold
S. Reinhardt
A. Dahl
N. S. Anstee
R. Bogeska
M. D. Milsom
P. Sawen
H. X. Wan
David Bryder
A. Roers
A. Gerbaulet
Published in Journal of Experimental Medicine
Volume 217
Issue 6
Pages 18
ISSN 0022-1007
Publication year 2020
Published at Sahlgrenska Cancer Center
Pages 18
Language en
Links dx.doi.org/10.1084/jem.20191284
Keywords self-renewal, gene-expression, dynamics, exchange, proliferation, heterogeneity, history, cd34, h3, Immunology, Research & Experimental Medicine
Subject categories Immunology in the medical area

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 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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