School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084
Zhenzhen Zhang
School of Medicine, Tsinghua University, Beijing 100084
Hanqing He
School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084
Jinghui Song
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
Yang Cui
School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084
Yunan Chen
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing
Yuan Zhuang
Department of Basic Medical Sciences, School of Medicine, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, THU-PKU Center for Life Sciences, Tsinghua University, Beijing
Xiaoting Zhang
Department of Basic Medical Sciences, School of Medicine, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, THU-PKU Center for Life Sciences, Tsinghua University, Beijing
Mo Li
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191
Xinxiang Zhang
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing
Michael Q. Zhang
School of Medicine, Tsinghua University, Beijing 100084, China; MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic and Systems Biology, BNRist; Department of Automation, Tsinghua University, Beijing 100084, China; Department of Biological Sciences, Center for Systems Biology, the University of Texas, Richardson, TX 75080-3021
Minglei Shi
School of Medicine, Tsinghua University, Beijing 100084
Chengqi Yi
Department of Basic Medical Sciences, School of Medicine, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, THU-PKU Center for Life Sciences, Tsinghua University, Beijing
Jianwei Wang
School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084
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.
