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Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta

Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis iden...

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Autores principales: Chen, Yang, Yang, Sujuan, Lovisa, Sara, Ambrose, Catherine G., McAndrews, Kathleen M., Sugimoto, Hikaru, Kalluri, Raghu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664945/
https://www.ncbi.nlm.nih.gov/pubmed/34893625
http://dx.doi.org/10.1038/s41467-021-27563-3
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author Chen, Yang
Yang, Sujuan
Lovisa, Sara
Ambrose, Catherine G.
McAndrews, Kathleen M.
Sugimoto, Hikaru
Kalluri, Raghu
author_facet Chen, Yang
Yang, Sujuan
Lovisa, Sara
Ambrose, Catherine G.
McAndrews, Kathleen M.
Sugimoto, Hikaru
Kalluri, Raghu
author_sort Chen, Yang
collection PubMed
description Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap(+) cells and Fsp1(+) cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap(+) cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1(+) cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta.
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spelling pubmed-86649452021-12-27 Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta Chen, Yang Yang, Sujuan Lovisa, Sara Ambrose, Catherine G. McAndrews, Kathleen M. Sugimoto, Hikaru Kalluri, Raghu Nat Commun Article Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap(+) cells and Fsp1(+) cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap(+) cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1(+) cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta. Nature Publishing Group UK 2021-12-10 /pmc/articles/PMC8664945/ /pubmed/34893625 http://dx.doi.org/10.1038/s41467-021-27563-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Yang
Yang, Sujuan
Lovisa, Sara
Ambrose, Catherine G.
McAndrews, Kathleen M.
Sugimoto, Hikaru
Kalluri, Raghu
Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title_full Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title_fullStr Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title_full_unstemmed Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title_short Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
title_sort type-i collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and osteogenesis imperfecta
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664945/
https://www.ncbi.nlm.nih.gov/pubmed/34893625
http://dx.doi.org/10.1038/s41467-021-27563-3
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