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Identification of fibroblast progenitors in the developing mouse thymus
The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus;...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188757/ https://www.ncbi.nlm.nih.gov/pubmed/35587733 http://dx.doi.org/10.1242/dev.200513 |
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author | Ferreirinha, Pedro Pinheiro, Ruben G. R. Landry, Jonathan J. M. Alves, Nuno L. |
author_facet | Ferreirinha, Pedro Pinheiro, Ruben G. R. Landry, Jonathan J. M. Alves, Nuno L. |
author_sort | Ferreirinha, Pedro |
collection | PubMed |
description | The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αβ(+)GP38(+)SCA-1(−) cells prevailed in the embryonic thymus and declined thereafter, CD140αβ(+)GP38(+)SCA-1(+) cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αβ(+)GP38(+)SCA-1(+) cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αβ(+)GP38(+)SCA-1(+) maintained their phenotype in thymic organoids. Strikingly, CD140αβ(+)GP38(+)SCA-1(−) generated CD140αβ(+)GP38(+)SCA-1(+), inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αβ(+)GP38(+)SCA-1(+) fibroblasts was gradually reduced in Rag2(−/−) and Rag2(−/−)Il2rg(−/−) thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αβ(+)GP38(+)SCA-1(−) as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation. |
format | Online Article Text |
id | pubmed-9188757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-91887572022-07-01 Identification of fibroblast progenitors in the developing mouse thymus Ferreirinha, Pedro Pinheiro, Ruben G. R. Landry, Jonathan J. M. Alves, Nuno L. Development Research Report The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αβ(+)GP38(+)SCA-1(−) cells prevailed in the embryonic thymus and declined thereafter, CD140αβ(+)GP38(+)SCA-1(+) cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αβ(+)GP38(+)SCA-1(+) cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αβ(+)GP38(+)SCA-1(+) maintained their phenotype in thymic organoids. Strikingly, CD140αβ(+)GP38(+)SCA-1(−) generated CD140αβ(+)GP38(+)SCA-1(+), inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αβ(+)GP38(+)SCA-1(+) fibroblasts was gradually reduced in Rag2(−/−) and Rag2(−/−)Il2rg(−/−) thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αβ(+)GP38(+)SCA-1(−) as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation. The Company of Biologists Ltd 2022-05-26 /pmc/articles/PMC9188757/ /pubmed/35587733 http://dx.doi.org/10.1242/dev.200513 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Report Ferreirinha, Pedro Pinheiro, Ruben G. R. Landry, Jonathan J. M. Alves, Nuno L. Identification of fibroblast progenitors in the developing mouse thymus |
title | Identification of fibroblast progenitors in the developing mouse thymus |
title_full | Identification of fibroblast progenitors in the developing mouse thymus |
title_fullStr | Identification of fibroblast progenitors in the developing mouse thymus |
title_full_unstemmed | Identification of fibroblast progenitors in the developing mouse thymus |
title_short | Identification of fibroblast progenitors in the developing mouse thymus |
title_sort | identification of fibroblast progenitors in the developing mouse thymus |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188757/ https://www.ncbi.nlm.nih.gov/pubmed/35587733 http://dx.doi.org/10.1242/dev.200513 |
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