Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
Yuqian Wang1, Zhenzhen Zhang2, Hanqing He1
1School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084.
Haematologica
|May 11, 2023
Summary
Aging impairs hematopoietic stem cells (HSC). Increased pseudouridine synthase 10 (PUS10) in aged HSC is linked to functional decline, offering potential for HSC rejuvenation therapies.
Area of Science:
- Hematology
- Stem Cell Biology
- Molecular Gerontology
Background:
- Aged hematopoietic stem cells (HSC) show reduced function and myeloid bias.
- The underlying molecular mechanisms of HSC aging are not fully understood.
Purpose of the Study:
- To investigate the role of pseudouridine (Ψ) synthase 10 (PUS10) in HSC aging.
- To elucidate the molecular mechanisms linking PUS10 to HSC dysfunction in aging.
Main Methods:
- Assessed PUS10 expression in young and aged hematopoietic stem and progenitor cells (HSPC).
- Utilized PUS10 overexpression and knockout mouse models (Pus10-/-).
- Examined RNA pseudouridylation profiles and CRL4DCAF1-mediated ubiquitination of PUS10.
Main Results:
- PUS10 expression is elevated in aged HSPC.
- Enforced PUS10 expression mimicked aged HSC phenotype, independent of its enzymatic activity.
- Aged Pus10-/- mice showed mild hematopoietic alterations, while young ones did not.
- Aging-induced increase in PUS10 is attributed to decreased CRL4DCAF1-mediated degradation.
Conclusions:
- PUS10 plays a significant role in HSC aging and function.
- The CRL4DCAF1-PUS10 ubiquitination pathway is a key regulator of HSC aging.
- Findings offer novel insights into HSC rejuvenation and potential clinical applications.
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