成骨细胞
细胞生物学
血管生成
生物
电池类型
体内
细胞
癌症研究
体外
遗传学
作者
Yun Gong,Jin Yang,Xiaohua Li,Chaohui Zhou,Chen Yu,Zun Wang,Xiang Qiu,Ying Liu,Huixi Zhang,Jonathan Greenbaum,Liang Cheng,Yihe Hu,Jie Xie,Xuecheng Yang,Yusheng Li,Yuntong Bai,Yuping Wang,Yiping Chen,Lijun Tan,Hui Shen,Hong‐Mei Xiao,Hong‐Wen Deng
出处
期刊:Aging
[Impact Journals, LLC]
日期:2021-08-24
卷期号:13 (16): 20629-20650
被引量:19
标识
DOI:10.18632/aging.203452
摘要
Human osteoblasts are multifunctional bone cells, which play essential roles in bone formation, angiogenesis regulation, as well as maintenance of hematopoiesis. However, the categorization of primary osteoblast subtypes in vivo in humans has not yet been achieved. Here, we used single-cell RNA sequencing (scRNA-seq) to perform a systematic cellular taxonomy dissection of freshly isolated human osteoblasts from one 31-year-old male with osteoarthritis and osteopenia after hip replacement. Based on the gene expression patterns and cell lineage reconstruction, we identified three distinct cell clusters including preosteoblasts, mature osteoblasts, and an undetermined rare osteoblast subpopulation. This novel subtype was found to be the major source of the nuclear receptor subfamily 4 group A member 1 and 2 (NR4A1 and NR4A2) in primary osteoblasts, and the expression of NR4A1 was confirmed by immunofluorescence staining on mouse osteoblasts in vivo. Trajectory inference analysis suggested that the undetermined cluster, together with the preosteoblasts, are involved in the regulation of osteoblastogenesis and also give rise to mature osteoblasts. Investigation of the biological processes and signaling pathways enriched in each subpopulation revealed that in addition to bone formation, preosteoblasts and undetermined osteoblasts may also regulate both angiogenesis and hemopoiesis. Finally, we demonstrated that there are systematic differences between the transcriptional profiles of human and mouse osteoblasts, highlighting the necessity for studying bone physiological processes in humans rather than solely relying on mouse models. Our findings provide novel insights into the cellular heterogeneity and potential biological functions of human primary osteoblasts at the single-cell level.
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