Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
Yuqian Wang1, Zhenzhen Zhang2, Hanqing He1
1School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084.
Abstract:
Aged hematopoietic stem cells (HSC) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage, however, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of transcribed RNA pseudouridylation profile between young and aged HSPC. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/- mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided a novel insight into HSC rejuvenation and its clinical application.
More Related Videos
11:06Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
07:17Improving the Accuracy of Flow Cytometric Assessment of Mitochondrial Membrane Potential in Hematopoietic Stem and Progenitor Cells Through the Inhibition of Efflux Pumps
Published on: July 30, 2019
Related Concept Videos
Multipotency of Hematopoietic Stem Cells
Regulation of Hematopoietic Stem Cells
Unrenewable Cells
Photoreceptors
The retina is composed of several layers and contains specialized cells called photoreceptors. The photoreceptors (rods and cones) change their membrane potential when stimulated by light energy. There are two types of photoreceptors—rods and cones—which differ in the shape of...
iPS Cell Differentiation
Hematopoiesis
Biosynthesis of Nucleic Acids
