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

来源：

ISCIENCE | 2024年 / 27卷 / 09期

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.

引用

页数：22

共 76 条

[11] Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse [J].