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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2023
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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. |
format | Online Article Text |
id | pubmed-10542847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
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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