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A systematic dissection of human primary osteoblasts in vivo at single-cell resolution
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 sequ...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436943/ https://www.ncbi.nlm.nih.gov/pubmed/34428745 http://dx.doi.org/10.18632/aging.203452 |
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author | Gong, Yun Yang, Junxiao Li, Xiaohua Zhou, Cui Chen, Yu Wang, Zun Qiu, Xiang Liu, Ying Zhang, Huixi Greenbaum, Jonathan Cheng, Liang Hu, Yihe Xie, Jie Yang, Xuecheng Li, Yusheng Bai, Yuntong Wang, Yu-Ping Chen, Yiping Tan, Li-Jun Shen, Hui Xiao, Hong-Mei Deng, Hong-Wen |
author_facet | Gong, Yun Yang, Junxiao Li, Xiaohua Zhou, Cui Chen, Yu Wang, Zun Qiu, Xiang Liu, Ying Zhang, Huixi Greenbaum, Jonathan Cheng, Liang Hu, Yihe Xie, Jie Yang, Xuecheng Li, Yusheng Bai, Yuntong Wang, Yu-Ping Chen, Yiping Tan, Li-Jun Shen, Hui Xiao, Hong-Mei Deng, Hong-Wen |
author_sort | Gong, Yun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8436943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-84369432021-09-14 A systematic dissection of human primary osteoblasts in vivo at single-cell resolution Gong, Yun Yang, Junxiao Li, Xiaohua Zhou, Cui Chen, Yu Wang, Zun Qiu, Xiang Liu, Ying Zhang, Huixi Greenbaum, Jonathan Cheng, Liang Hu, Yihe Xie, Jie Yang, Xuecheng Li, Yusheng Bai, Yuntong Wang, Yu-Ping Chen, Yiping Tan, Li-Jun Shen, Hui Xiao, Hong-Mei Deng, Hong-Wen Aging (Albany NY) Research Paper 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. Impact Journals 2021-08-24 /pmc/articles/PMC8436943/ /pubmed/34428745 http://dx.doi.org/10.18632/aging.203452 Text en Copyright: © 2021 Gong et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gong, Yun Yang, Junxiao Li, Xiaohua Zhou, Cui Chen, Yu Wang, Zun Qiu, Xiang Liu, Ying Zhang, Huixi Greenbaum, Jonathan Cheng, Liang Hu, Yihe Xie, Jie Yang, Xuecheng Li, Yusheng Bai, Yuntong Wang, Yu-Ping Chen, Yiping Tan, Li-Jun Shen, Hui Xiao, Hong-Mei Deng, Hong-Wen A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title | A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title_full | A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title_fullStr | A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title_full_unstemmed | A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title_short | A systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
title_sort | systematic dissection of human primary osteoblasts in vivo at single-cell resolution |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436943/ https://www.ncbi.nlm.nih.gov/pubmed/34428745 http://dx.doi.org/10.18632/aging.203452 |
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