PT  - JOURNAL ARTICLE
AU  - Mina N. F. Morcos
AU  - Thomas Zerjatke
AU  - Ingmar Glauche
AU  - Clara M. Munz
AU  - Yan Ge
AU  - Andreas Petzold
AU  - Susanne Reinhardt
AU  - Andreas Dahl
AU  - Natasha Anstee
AU  - Ruzhica Bogeska
AU  - Michael Milsom
AU  - Petter Säwén
AU  - Haixia Wan
AU  - David Bryder
AU  - Axel Roers
AU  - Alexander Gerbaulet
TI  - Proliferative behavior of hematopoietic stem cells revisited: No evidence for mitotic memory
AID  - 10.1101/745729
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 745729
4099  - http://biorxiv.org/content/early/2019/08/28/745729.short
4100  - http://biorxiv.org/content/early/2019/08/28/745729.full
AB  - The proliferative activity of adult 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 the most primitive HSCs 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 primitive HSCs with high repopulation potential. We argue that this background had been misinterpreted as retention of induced label and permanent quiescence. 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 HSC mitotic memory and entry into permanent quiescence after few divisions, but show that primitive HSCs of adult mice continue to cycle rarely.