Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
Open Access
- 16 April 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 217 (6)
- https://doi.org/10.1084/jem.20191284
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.Keywords
Funding Information
- German Research Council (DFG, GE3038/1-1)
- German Research Council (RO2133/10-1, FOR2577)
- Dresden International Graduate School for Biomedicine and Bioengineering
- German Research Council
- German Federal Ministry of Education and Research (031A315)
- Tobias Foundation
- Swedish Cancer Society
This publication has 51 references indexed in Scilit:
- Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammationThe Journal of Experimental Medicine, 2011
- Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansionProceedings of the National Academy of Sciences of the United States of America, 2010
- Fast and SNP-tolerant detection of complex variants and splicing in short readsBioinformatics, 2010
- Stem Cell Proliferation and Quiescence—Two Sides of the Same CoinPLoS Computational Biology, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cellsNature Biotechnology, 2008
- Promiscuous Expression of H2B-GFP Transgene in Hematopoietic Stem CellsPLOS ONE, 2008
- Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cellsThe EMBO Journal, 2008
- Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdUNature, 2007
- Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defectJCI Insight, 2006