Continuous mitotic activity of primitive hematopoietic stem cells in adult mice

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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.

Details

Original languageEnglish
Article numbere20191284
JournalThe Journal of experimental medicine
Volume217
Issue number6
Publication statusPublished - 1 Jun 2020
Peer-reviewedYes

External IDs

PubMedCentral PMC7971128
Scopus 85086649899
ORCID /0000-0001-9599-8632/work/142241737
ORCID /0000-0002-2524-1199/work/142251502

Keywords

Keywords

  • Aging/physiology, Animals, Fluorescence, Gene Expression Regulation, Hematopoietic Stem Cells/cytology, Histones/metabolism, Kinetics, Mice, Inbred C57BL, Mitosis, Models, Biological, Proteolysis, Recombinant Fusion Proteins/metabolism