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Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells

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收录情况： ◇ SCIE

作者：
He Hanqing[1] * ; Wang Yuqian[1] * ; Zhang Xiaoting[2] * ; Li Xiaoyu[2] * ; Liu Chao[3] ; Yan Dingfei[4] ; Deng Haiteng[4] ; Sun Wanling[5] ; Yi Chengqi[2,6] ; Wang Jianwei[1,7] ;
机构： [1]School of Pharmaceutical Sciences, Tsinghua University, Beijing, China. [2]State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. [3]Department of Laboratory Animal Science, Hebei Key Lab of Hebei Laboratory Animal Science, Hebei Medical University, Shijiazhuang, P. R. China. [4]MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China. [5]Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China. [6]State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. [7]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
出处：
DOI： 10.1038/s43587-023-00556-1

摘要：
Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation bias toward myeloid lineages. However, the molecular mechanism behind HSC aging remains largely unknown. In this study, we observed that RNA N1-methyladenosine-generating methyltransferase TRMT6-TRMT61A complex is increased in aged murine HSCs due to aging-declined CRL4DCAF1-mediated ubiquitination degradation signaling. Unexpectedly, no difference of tRNA N1-methyladenosine methylome is observed between young and aged hematopoietic stem and progenitor cells, suggesting a noncanonical role of the TRMT6-TRMT61A complex in the HSC aging process. Further investigation revealed that enforced TRMT6-TRMT61A impairs HSCs through 3'-tiRNA-Leu-CAG and subsequent RIPK1-RIPK3-MLKL-mediated necroptosis cascade. Deficiency of necroptosis ameliorates the self-renewal capacity of HSCs and counters the physiologically deleterious effect of enforced TRMT6-TRMT61A on HSCs. Together, our work uncovers a nonclassical role for the TRMT6-TRMT61A complex in HSC aging and highlights a therapeutic target.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

基金：
grant numbers 82250002, 92249305, Z200022 and 2018YFA0800200 to J.W. from the National Key R&D Program of China or the Beijing Municipal Science & Technology Commission and the National Natural Science Foundation of China. This work was also supported by the National Key R&D Program of China (nos. 2019YFA0802200 and 2019YFA0110900) and the National Natural Science Foundation of China (nos. 91940304, 31861143026 and 21825701 to C.Y.).
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外文
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出版当年[2023]版：
无
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大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 老年医学 1 区 神经科学
JCR分区：
出版当年[2022]版：
无
最新[2024]版：
Q1 CELL BIOLOGY Q1 GERIATRICS & GERONTOLOGY Q1 NEUROSCIENCES

影响因子： 最新[2024版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
共同第一作者：
通讯作者：
通讯机构： [1]School of Pharmaceutical Sciences, Tsinghua University, Beijing, China. [2]State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. [6]State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. [7]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
推荐引用方式(GB/T 7714)：
He Hanqing,Wang Yuqian,Zhang Xiaoting,et al.Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells[J].NATURE AGING.2024,4(2):doi:10.1038/s43587-023-00556-1.
APA：
He Hanqing,Wang Yuqian,Zhang Xiaoting,Li Xiaoyu,Liu Chao...&Wang Jianwei.(2024).Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells.NATURE AGING,4,(2)
MLA：
He Hanqing,et al."Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells".NATURE AGING 4..2(2024)

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