机构：[1]Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 310036, China[2]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy ofSciences, Beijing 100101, China[3]Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, Guangdong 510632, China[4]Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, BeijingEngineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseasesof Ministry of Education, Beijing 100053, China科技平台神经变性病教育部重点实验室首都医科大学宣武医院[5]School of Rehabilitation Medicine, Weifang Medical University, Weifang, Shandong 261053, China[6]Division of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA[7]University of Chinese Academy of Sciences, Beijing 100049, China[8]Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor(-/-) HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor(-/-) HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.
基金：
National Key RD Program [2016YFA0100602, 2017YFA0103302, 2017YFA0504000, 2020YFA0112404]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91749203, 82030039, 92049304, 31570857, 31701203, 81901403, 91849203, 92049112]; Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110103002]; Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S347]; Zhejiang Province College Students' Science and Technology Innovation Activities [2018R413067]; Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDB39000000]
第一作者机构：[1]Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 310036, China
共同第一作者：
通讯作者：
通讯机构：[2]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy ofSciences, Beijing 100101, China[7]University of Chinese Academy of Sciences, Beijing 100049, China[8]Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
推荐引用方式(GB/T 7714)：
Yi Weiwei,Zhang Yuying,Liu Bo,et al.Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration[J].CELL REPORTS.2021,34(13):doi:10.1016/j.celrep.2021.108922.
APA：
Yi, Weiwei,Zhang, Yuying,Liu, Bo,Zhou, Yuanyuan,Liao, Dandan...&Ju, Zhenyu.(2021).Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration.CELL REPORTS,34,(13)
MLA：
Yi, Weiwei,et al."Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration".CELL REPORTS 34..13(2021)
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