Sleep exerts lasting effects on hematopoietic stem cell function and diversity

Area of Science:

• Hematology
• Epigenetics
• Sleep Science

Background:

• Sleep's restorative functions are substantial, yet prolonged effects of sleep disruption remain unclear.
• While catch-up sleep partially mitigates sleep debt, its long-term impact on cellular mechanisms is not fully understood.

Purpose of the Study:

• To investigate the impact of sleep interruption on the epigenome of hematopoietic stem and progenitor cells (HSPCs).
• To elucidate the mechanisms by which sleep influences hematopoietic clonal diversity and inflammatory responses.

Main Methods:

• Analysis of HSPC epigenome changes following sleep interruption.
• Hematopoietic clonal tracking and mathematical modeling to assess clonal diversity and genetic drift.
• Investigation of HSPC proliferation and cell fate commitment (myeloid skewing).

Main Results:

• Sleep interruption restructures the HSPC epigenome, increasing proliferation and accelerating genetic drift.
• Sleep fragmentation leads to reduced hematopoietic clonal diversity and skews cell commitment toward a myeloid fate.
• Sleep restriction in humans also alters the HSPC epigenome and activates hematopoiesis, priming for inflammation.

Conclusions:

• Sleep is essential for maintaining hematopoietic system integrity by regulating the HSPC epigenome.
• Sleep calibrates the hematopoietic epigenome, constrains inflammatory output, and preserves clonal diversity, slowing system decay.
• Findings highlight the critical role of sleep in preventing accelerated aging and inflammatory diseases originating from hematopoietic stem cells.