Single-cell multi-omics identify novel regulators required for osteoclastogenesis during aging

被引:1
作者
Li, Hao [1 ]
Xu, Wan-Xing [2 ]
Tan, Jing-Cong [2 ]
Hong, Yue-Mei [2 ]
He, Jian [2 ]
Zhao, Ben-Peng [2 ]
Zhou, Jin-An [2 ]
Zheng, Yu-Min [4 ,5 ]
Lei, Ming [3 ]
Zheng, Xiao-Qi [2 ]
Ding, Jun [4 ,5 ]
Lu, Ning-Ning [2 ]
Gao, Jun-Jie [1 ,6 ]
Zhang, Chang-Qing [1 ]
Wang, Hui [2 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Orthopaed, Sch Med, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Ctr Single Cell Om, Sch Publ Hlth, State Key Lab Syst Med Canc,Sch Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Peoples Hosp 9, Shanghai Inst Precis Med, Sch Med, Shanghai, Peoples R China
[4] McGill Univ, Fac Med & Hlth Sci, Quantitat Life Sci, Montreal, PQ, Canada
[5] McGill Univ, Dept Med, Meakins Christie Labs, Hlth Ctr, Montreal, PQ, Canada
[6] Shanghai Sixth Peoples Hosp Fujian, 16 Luoshan Sect,Jinguang Rd,Luoshan St, Quanzhou, Fujian, Peoples R China
基金
加拿大自然科学与工程研究理事会; 中国国家自然科学基金; 国家重点研发计划;
关键词
OSTEOBLAST DIFFERENTIATION; BONE LOSS; EXPRESSION; IDENTIFICATION; POPULATION; INHIBITION; ACTIVATION; ALIGNMENT; NETWORKS; LINES;
D O I
10.1016/j.isci.2024.110734
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Age-related osteoporosis manifests as a complex pathology that disrupts bone homeostasis and elevates fracture risk, yet the mechanisms facilitating age-related shifts in bone marrow macrophages/osteoclasts (BMMs/OCs) lineage are not fully understood. To decipher these mechanisms, we conducted an investigation into the determinants controlling BMMs/OCs differentiation. We performed single-cell multi-omics profiling on bone marrow samples from mice of different ages (1, 6, and 20 months) to gain a holistic understanding of cellular changes across time. Our analysis revealed that aging significantly instigates OC differentiation. Importantly, we identified Cebpd as a vital gene for osteoclastogenesis and bone resorption during the aging process. Counterbalancing the effects of Cebpd, , we found Irf8, , Sox4, , and Klf4 to play crucial roles. By thoroughly examining the cellular dynamics underpinning bone aging, our study unveils novel insights into the mechanisms of age-related osteoporosis and presents potential therapeutic targets for future exploration.
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页数:22
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