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Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE213422 | GEO | 2023/05/13

REPOSITORIES: GEO

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Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

Project description:Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage. However, the molecular mechanism behind it remains not fully understood. In this study, we evaluated the expression of 5 pseudouridine (Ψ) synthases between young and aged HSCs, and observed that three of them are increased during aging. Functional evaluation assay reveals that enforced PUS10 and PUS7 recapitulate the phenotype aged HSCs. The increase of PUS10 in aged HSCs is due to aging-declined CRL4DCAF1-mediated ubiquitination degradation signaling. Mechanistically, the destructive role of enforced PUS10 on HSCs is not achieved by its Ψ synthases activity, but through miR139, dysfunction of which impairs the reconstitution capacity of HSCs. Consistently, we observed no difference of tRNA pseudouridylation profile between young and aged HSPCs, while enforced PUS10 alters the microRNA profile in HSCs. Targeted dysfunction of Pus10 results in compromises the self-renewal capacity of HSC.

2023-05-13 | GSE213421 | GEO

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

2023-05-13 | GSE213420 | GEO

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

2023-05-13 | GSE213419 | GEO

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

Project description:Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage. While, 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 (HSPCs) and enforced PUS10 recapitulates the phenotype of aged HSCs, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of tRNA pseudouridylation profile between young and aged HSPCs. 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 HSPCs 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 novel insight for HSC rejuvenation and clinical application.

2023-05-13 | GSE213417 | GEO

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells