Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis

Abstract With the aging of the population, the incidence of osteoporosis (OP) is on the rise, but the ecology of immune cell subpopulations in OP is poorly understood. Therefore, identifying cell subpopulations involved in promoting the development of OP may facilitate the development of new treatme...

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Main Authors: Weiwei Yang, Yulin Wang, Ke Mo, Wenyang Chen, Xiangtao Xie
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-80993-z
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author Weiwei Yang
Yulin Wang
Ke Mo
Wenyang Chen
Xiangtao Xie
author_facet Weiwei Yang
Yulin Wang
Ke Mo
Wenyang Chen
Xiangtao Xie
author_sort Weiwei Yang
collection DOAJ
description Abstract With the aging of the population, the incidence of osteoporosis (OP) is on the rise, but the ecology of immune cell subpopulations in OP is poorly understood. Therefore, identifying cell subpopulations involved in promoting the development of OP may facilitate the development of new treatments. Based on bioinformatics analysis, we constructed a single-cell landscape of the OP microenvironment and identified immune cell subpopulations in OP to further explore the role of different subpopulations in the abnormal bone microenvironment. Among macrophages (Mac), the Mac_OLR1 subpopulation has an M1-like phenotype and significantly activates cytokine and osteoclast differentiation pathways, interacting with osteoclasts via the HBEGF-CD9 axis. In neutrophils (Neut), the Neut_RSAD2 subpopulation significantly activated cytokine and osteoclast differentiation pathways and had a high neutrophil extracellular trap (NET) score, and H1FX was identified as its potential regulator. In effector memory T (Tem) cells, the Tem_CCL4 subpopulation significantly activated osteoclast differentiation and immune inflammation-related pathways and highly expressed proinflammatory molecules such as CCL4, CCL4L2, CCL5 and IFNG. In B cells, the abundance of the B_ACSM3 subpopulation was significantly increased in the OP group and the osteoclast differentiation pathway was significantly activated, and MYB was identified as its potential regulator. In summary, we identified several immune cell subpopulations that may be involved in promoting the formation of OP, further identified the transcription factors that regulate these subpopulations, and speculated that the development of OP may be accompanied by immune inflammatory responses mediated by these subpopulations. These findings provide candidate molecules and cells for future OP research and may help facilitate the development of new therapies.
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spelling doaj-art-5a7f5faa4f5f481890b3c222213582fa2025-08-20T02:08:24ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-80993-zSingle-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosisWeiwei Yang0Yulin Wang1Ke Mo2Wenyang Chen3Xiangtao Xie4Department of Gynecology, The Fourth Affiliated Hospital of Guangxi Medical UniversityDepartment of Orthopedics, The Fourth Affiliated Hospital of Guangxi Medical UniversityClinical Research Center, The Second Affiliated Hospital of Guangxi Medical UniversityDepartment of Orthopedics, Liuzhou People’s HospitalDepartment of Orthopedics, The Fourth Affiliated Hospital of Guangxi Medical UniversityAbstract With the aging of the population, the incidence of osteoporosis (OP) is on the rise, but the ecology of immune cell subpopulations in OP is poorly understood. Therefore, identifying cell subpopulations involved in promoting the development of OP may facilitate the development of new treatments. Based on bioinformatics analysis, we constructed a single-cell landscape of the OP microenvironment and identified immune cell subpopulations in OP to further explore the role of different subpopulations in the abnormal bone microenvironment. Among macrophages (Mac), the Mac_OLR1 subpopulation has an M1-like phenotype and significantly activates cytokine and osteoclast differentiation pathways, interacting with osteoclasts via the HBEGF-CD9 axis. In neutrophils (Neut), the Neut_RSAD2 subpopulation significantly activated cytokine and osteoclast differentiation pathways and had a high neutrophil extracellular trap (NET) score, and H1FX was identified as its potential regulator. In effector memory T (Tem) cells, the Tem_CCL4 subpopulation significantly activated osteoclast differentiation and immune inflammation-related pathways and highly expressed proinflammatory molecules such as CCL4, CCL4L2, CCL5 and IFNG. In B cells, the abundance of the B_ACSM3 subpopulation was significantly increased in the OP group and the osteoclast differentiation pathway was significantly activated, and MYB was identified as its potential regulator. In summary, we identified several immune cell subpopulations that may be involved in promoting the formation of OP, further identified the transcription factors that regulate these subpopulations, and speculated that the development of OP may be accompanied by immune inflammatory responses mediated by these subpopulations. These findings provide candidate molecules and cells for future OP research and may help facilitate the development of new therapies.https://doi.org/10.1038/s41598-024-80993-zSingle-cell sequencingAbnormal bone microenvironmentImmune cellsCell communicationOsteoporosis
spellingShingle Weiwei Yang
Yulin Wang
Ke Mo
Wenyang Chen
Xiangtao Xie
Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
Scientific Reports
Single-cell sequencing
Abnormal bone microenvironment
Immune cells
Cell communication
Osteoporosis
title Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
title_full Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
title_fullStr Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
title_full_unstemmed Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
title_short Single-cell RNA sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
title_sort single cell rna sequencing reveals multiple immune cell subpopulations promote the formation of abnormal bone microenvironment in osteoporosis
topic Single-cell sequencing
Abnormal bone microenvironment
Immune cells
Cell communication
Osteoporosis
url https://doi.org/10.1038/s41598-024-80993-z
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AT kemo singlecellrnasequencingrevealsmultipleimmunecellsubpopulationspromotetheformationofabnormalbonemicroenvironmentinosteoporosis
AT wenyangchen singlecellrnasequencingrevealsmultipleimmunecellsubpopulationspromotetheformationofabnormalbonemicroenvironmentinosteoporosis
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