G2 arrest primes hematopoietic stem cells for megakaryopoiesis

Published: 5 June 2024| Version 1 | DOI: 10.17632/ztwnydbhsw.1
Contributor:
Hans Snoeck

Description

In contrast to most hematopoietic lineages, megakaryocytes (MKs) can derive rapidly and directly from hematopoietic stem cells (HSCs). The underlying mechanism is unclear however. Here we show that DNA damage induces MK markers in HSCs and that G2 arrest, an integral part of the DNA damage response, suffices for MK priming followed by irreversible MK differentiation in HSCs, but not in progenitors. We also show that replication stress causes DNA damage in HSCs and is at least in part due to uracil misincorporation in vitro and in vivo. Consistent with this notion, thymidine attenuated DNA damage, improved HSC maintenance and reduced the generation of CD41+ MK-committed HSCs. Replication stress and concomitant MK differentiation is therefore one of the barriers to HSC maintenance. DNA damage-induced MK priming may allow rapid generation of a lineage essential to immediate organismal survival, while also removing damaged cells from the HSC pool. This dataset accompanies a manuscript in Cell Report, 2024, and contain the data from

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Steps to reproduce

Please see publication: G2 arrest primes hematopoietic stem cells for megakaryopoiesis, Cell Report 2024, in press

Institutions

Columbia University

Categories

Cell Cycle, DNA Damage Response, Hematopoietic Stem Cell, General Hematopoiesis, Megakaryocytopoiesis

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