Sleep exerts lasting effects on hematopoietic stem cell function and diversity

Cameron S. McAlpine, Máté G. Kiss, Faris M. Zuraikat, David Cheek, Giulia Schiroli, Hajera Amatullah, Pacific Huynh, Mehreen Z. Bhatti, Lai Ping Wong, Abi G. Yates, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Henrike Janssen, Jeffrey Downey, Sumnima Singh, Ruslan I. Sadreyev, Matthias Nahrendorf, Kate L. Jeffrey, David T. ScaddenKamila Naxerova, Marie Pierre St-Onge, Filip K. Swirski

Research output: Contribution to journalArticlepeer-review

Abstract

A sleepless night may feel awful in its aftermath, but sleep's revitalizing powers are substantial, perpetuating the idea that convalescent sleep is a consequence-free physiological reset. Although recent studies have shown that catch-up sleep insufficiently neutralizes the negative effects of sleep debt, the mechanisms that control prolonged effects of sleep disruption are not understood. Here, we show that sleep interruption restructures the epigenome of hematopoietic stem and progenitor cells (HSPCs) and increases their proliferation, thus reducing hematopoietic clonal diversity through accelerated genetic drift. Sleep fragmentation exerts a lasting influence on the HSPC epigenome, skewing commitment toward a myeloid fate and priming cells for exaggerated inflammatory bursts. Combining hematopoietic clonal tracking with mathematical modeling, we infer that sleep preserves clonal diversity by limiting neutral drift. In humans, sleep restriction alters the HSPC epigenome and activates hematopoiesis. These findings show that sleep slows decay of the hematopoietic system by calibrating the hematopoietic epigenome, constraining inflammatory output, and maintaining clonal diversity.

Original languageEnglish
JournalJournal of Experimental Medicine
Volume219
Issue number11
DOIs
StatePublished - 7 Nov 2022
Externally publishedYes

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