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Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells

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 a...

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Autores principales: Wang, Yuqian, Zhang, Zhenzhen, He, Hanqing, Song, Jinghui, Cui, Yang, Chen, Yunan, Zhuang, Yuan, Zhang, Xiaoting, Li, Mo, Zhang, Xinxiang, Zhang, Michael Q., Shi, Minglei, Yi, Chengqi, Wang, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542847/
https://www.ncbi.nlm.nih.gov/pubmed/37165848
http://dx.doi.org/10.3324/haematol.2022.282211
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author Wang, Yuqian
Zhang, Zhenzhen
He, Hanqing
Song, Jinghui
Cui, Yang
Chen, Yunan
Zhuang, Yuan
Zhang, Xiaoting
Li, Mo
Zhang, Xinxiang
Zhang, Michael Q.
Shi, Minglei
Yi, Chengqi
Wang, Jianwei
author_facet Wang, Yuqian
Zhang, Zhenzhen
He, Hanqing
Song, Jinghui
Cui, Yang
Chen, Yunan
Zhuang, Yuan
Zhang, Xiaoting
Li, Mo
Zhang, Xinxiang
Zhang, Michael Q.
Shi, Minglei
Yi, Chengqi
Wang, Jianwei
author_sort Wang, Yuqian
collection PubMed
description 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 CRL4(DCAF1) complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4(DCAF1)-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.
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spelling pubmed-105428472023-10-03 Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells Wang, Yuqian Zhang, Zhenzhen He, Hanqing Song, Jinghui Cui, Yang Chen, Yunan Zhuang, Yuan Zhang, Xiaoting Li, Mo Zhang, Xinxiang Zhang, Michael Q. Shi, Minglei Yi, Chengqi Wang, Jianwei Haematologica Article - Hematopoiesis 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 CRL4(DCAF1) complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4(DCAF1)-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. Fondazione Ferrata Storti 2023-05-11 /pmc/articles/PMC10542847/ /pubmed/37165848 http://dx.doi.org/10.3324/haematol.2022.282211 Text en Copyright© 2023 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article - Hematopoiesis
Wang, Yuqian
Zhang, Zhenzhen
He, Hanqing
Song, Jinghui
Cui, Yang
Chen, Yunan
Zhuang, Yuan
Zhang, Xiaoting
Li, Mo
Zhang, Xinxiang
Zhang, Michael Q.
Shi, Minglei
Yi, Chengqi
Wang, Jianwei
Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title_full Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title_fullStr Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title_full_unstemmed Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title_short Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
title_sort aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells
topic Article - Hematopoiesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542847/
https://www.ncbi.nlm.nih.gov/pubmed/37165848
http://dx.doi.org/10.3324/haematol.2022.282211
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