Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation
Abstract Health is dependent on the homeostasis of both inner and external microenvironments. The microbiota as the external microenvironment plays a critical role in regulation of several organ systems in mammals. However, it is unclear whether the microbiota regulates homeostasis of the skeletal s...
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doaj-e7c13de7086a49d3bcaef40fcc25839f2020-11-24T23:15:51ZengBMCStem Cell Research & Therapy1757-65122017-09-01811710.1186/s13287-017-0670-7Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulationE Xiao0Linhai He1Qiong Wu2Junxiang Li3Yang He4Lu Zhao5Shuo Chen6Jingang An7Yansong Liu8Chider Chen9Yi Zhang10Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyMOE Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, Tsinghua UniversityMOE Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, Tsinghua UniversityDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyChinese Academy of Sciences Shanghai Laboratory Animal CenterDepartment of Anatomy and Cell Biology, University of Pennsylvania, School of Dental MedicineDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyAbstract Health is dependent on the homeostasis of both inner and external microenvironments. The microbiota as the external microenvironment plays a critical role in regulation of several organ systems in mammals. However, it is unclear whether the microbiota regulates homeostasis of the skeletal system and bone marrow mesenchymal stem cells (BMMSCs). Here, using a well-established germ-free (GF) mouse model, we show that the microbiota significantly alters the stemness of BMMSCs in comparison to specific-pathogen-free (SPF)-derived BMMSCs. Colonization of GF mice with SPF microbiota (conventionalized (ConvD)) normalizes the proliferation and differentiation abilities of BMMSCs. On the other hand, normal microbiota is required to maintain immunomodulatory properties of BMMSCs through induction of activated T-cell apoptosis and cytokine secretion. GF-derived BMMSCs lose the capacity to ameliorate disease phenotypes in dextran sulfate sodium-induced experimental colitis mice. Mechanistically, single-cell RNA-sequencing analysis shows that ConvD BMMSCs have a similar gene expression pattern to SPF-derived BMMSCs, which have a distinct gene distribution from GF-derived BMMSCs.http://link.springer.com/article/10.1186/s13287-017-0670-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
E Xiao Linhai He Qiong Wu Junxiang Li Yang He Lu Zhao Shuo Chen Jingang An Yansong Liu Chider Chen Yi Zhang |
spellingShingle |
E Xiao Linhai He Qiong Wu Junxiang Li Yang He Lu Zhao Shuo Chen Jingang An Yansong Liu Chider Chen Yi Zhang Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation Stem Cell Research & Therapy |
author_facet |
E Xiao Linhai He Qiong Wu Junxiang Li Yang He Lu Zhao Shuo Chen Jingang An Yansong Liu Chider Chen Yi Zhang |
author_sort |
E Xiao |
title |
Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
title_short |
Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
title_full |
Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
title_fullStr |
Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
title_full_unstemmed |
Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
title_sort |
microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2017-09-01 |
description |
Abstract Health is dependent on the homeostasis of both inner and external microenvironments. The microbiota as the external microenvironment plays a critical role in regulation of several organ systems in mammals. However, it is unclear whether the microbiota regulates homeostasis of the skeletal system and bone marrow mesenchymal stem cells (BMMSCs). Here, using a well-established germ-free (GF) mouse model, we show that the microbiota significantly alters the stemness of BMMSCs in comparison to specific-pathogen-free (SPF)-derived BMMSCs. Colonization of GF mice with SPF microbiota (conventionalized (ConvD)) normalizes the proliferation and differentiation abilities of BMMSCs. On the other hand, normal microbiota is required to maintain immunomodulatory properties of BMMSCs through induction of activated T-cell apoptosis and cytokine secretion. GF-derived BMMSCs lose the capacity to ameliorate disease phenotypes in dextran sulfate sodium-induced experimental colitis mice. Mechanistically, single-cell RNA-sequencing analysis shows that ConvD BMMSCs have a similar gene expression pattern to SPF-derived BMMSCs, which have a distinct gene distribution from GF-derived BMMSCs. |
url |
http://link.springer.com/article/10.1186/s13287-017-0670-7 |
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