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Regional specialization and fate specification of bone stromal cells in skeletal development
Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage rela...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293626/ https://www.ncbi.nlm.nih.gov/pubmed/34260921 http://dx.doi.org/10.1016/j.celrep.2021.109352 |
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author | Sivaraj, Kishor K. Jeong, Hyun-Woo Dharmalingam, Backialakshmi Zeuschner, Dagmar Adams, Susanne Potente, Michael Adams, Ralf H. |
author_facet | Sivaraj, Kishor K. Jeong, Hyun-Woo Dharmalingam, Backialakshmi Zeuschner, Dagmar Adams, Susanne Potente, Michael Adams, Ralf H. |
author_sort | Sivaraj, Kishor K. |
collection | PubMed |
description | Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage relationship between BMSC subsets and their regulation by intrinsic and extrinsic factors are not well understood. Here, we show with mouse genetics, ex vivo cell differentiation assays, and transcriptional profiling that BMSCs from metaphysis (mpMSCs) and diaphysis (dpMSCs) are fundamentally distinct. Fate-tracking experiments and single-cell RNA sequencing indicate that bone-forming osteoblast lineage cells and dpMSCs, including leptin receptor-positive (LepR(+)) reticular cells in bone marrow, emerge from mpMSCs in the postnatal metaphysis. Finally, we show that BMSC fate is controlled by platelet-derived growth factor receptor β (PDGFRβ) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation. |
format | Online Article Text |
id | pubmed-8293626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82936262021-07-23 Regional specialization and fate specification of bone stromal cells in skeletal development Sivaraj, Kishor K. Jeong, Hyun-Woo Dharmalingam, Backialakshmi Zeuschner, Dagmar Adams, Susanne Potente, Michael Adams, Ralf H. Cell Rep Article Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage relationship between BMSC subsets and their regulation by intrinsic and extrinsic factors are not well understood. Here, we show with mouse genetics, ex vivo cell differentiation assays, and transcriptional profiling that BMSCs from metaphysis (mpMSCs) and diaphysis (dpMSCs) are fundamentally distinct. Fate-tracking experiments and single-cell RNA sequencing indicate that bone-forming osteoblast lineage cells and dpMSCs, including leptin receptor-positive (LepR(+)) reticular cells in bone marrow, emerge from mpMSCs in the postnatal metaphysis. Finally, we show that BMSC fate is controlled by platelet-derived growth factor receptor β (PDGFRβ) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation. Cell Press 2021-07-13 /pmc/articles/PMC8293626/ /pubmed/34260921 http://dx.doi.org/10.1016/j.celrep.2021.109352 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Sivaraj, Kishor K. Jeong, Hyun-Woo Dharmalingam, Backialakshmi Zeuschner, Dagmar Adams, Susanne Potente, Michael Adams, Ralf H. Regional specialization and fate specification of bone stromal cells in skeletal development |
title | Regional specialization and fate specification of bone stromal cells in skeletal development |
title_full | Regional specialization and fate specification of bone stromal cells in skeletal development |
title_fullStr | Regional specialization and fate specification of bone stromal cells in skeletal development |
title_full_unstemmed | Regional specialization and fate specification of bone stromal cells in skeletal development |
title_short | Regional specialization and fate specification of bone stromal cells in skeletal development |
title_sort | regional specialization and fate specification of bone stromal cells in skeletal development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293626/ https://www.ncbi.nlm.nih.gov/pubmed/34260921 http://dx.doi.org/10.1016/j.celrep.2021.109352 |
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