Adult mouse fibroblasts retain organ-specific transcriptomic identity
Organ fibroblasts are essential components of homeostatic and diseased tissues. They participate in sculpting the extracellular matrix, sensing the microenvironment, and communicating with other resident cells. Recent studies have revealed transcriptomic heterogeneity among fibroblasts within and be...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71008 |
| _version_ | 1811205326208237568 |
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| author | Elvira Forte Mirana Ramialison Hieu T Nim Madison Mara Jacky Y Li Rachel Cohn Sandra L Daigle Sarah Boyd Edouard G Stanley Andrew G Elefanty John Travis Hinson Mauro W Costa Nadia A Rosenthal Milena B Furtado |
| author_facet | Elvira Forte Mirana Ramialison Hieu T Nim Madison Mara Jacky Y Li Rachel Cohn Sandra L Daigle Sarah Boyd Edouard G Stanley Andrew G Elefanty John Travis Hinson Mauro W Costa Nadia A Rosenthal Milena B Furtado |
| author_sort | Elvira Forte |
| collection | DOAJ |
| description | Organ fibroblasts are essential components of homeostatic and diseased tissues. They participate in sculpting the extracellular matrix, sensing the microenvironment, and communicating with other resident cells. Recent studies have revealed transcriptomic heterogeneity among fibroblasts within and between organs. To dissect the basis of interorgan heterogeneity, we compare the gene expression of murine fibroblasts from different tissues (tail, skin, lung, liver, heart, kidney, and gonads) and show that they display distinct positional and organ-specific transcriptome signatures that reflect their embryonic origins. We demonstrate that expression of genes typically attributed to the surrounding parenchyma by fibroblasts is established in embryonic development and largely maintained in culture, bioengineered tissues and ectopic transplants. Targeted knockdown of key organ-specific transcription factors affects fibroblast functions, in particular genes involved in the modulation of fibrosis and inflammation. In conclusion, our data reveal that adult fibroblasts maintain an embryonic gene expression signature inherited from their organ of origin, thereby increasing our understanding of adult fibroblast heterogeneity. The knowledge of this tissue-specific gene signature may assist in targeting fibrotic diseases in a more precise, organ-specific manner. |
| first_indexed | 2024-04-12T03:29:04Z |
| format | Article |
| id | doaj.art-fdff1021c46d4d60aff391d8030addd1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T03:29:04Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fdff1021c46d4d60aff391d8030addd12022-12-22T03:49:36ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.71008Adult mouse fibroblasts retain organ-specific transcriptomic identityElvira Forte0https://orcid.org/0000-0002-5555-9122Mirana Ramialison1https://orcid.org/0000-0001-6315-4777Hieu T Nim2Madison Mara3Jacky Y Li4Rachel Cohn5Sandra L Daigle6Sarah Boyd7Edouard G Stanley8Andrew G Elefanty9John Travis Hinson10Mauro W Costa11Nadia A Rosenthal12Milena B Furtado13https://orcid.org/0000-0003-1387-325XThe Jackson Laboratory, Bar Harbor, United StatesAustralian Regenerative Medicine Institute, Monash University, Clayton, Australia; Systems Biology Institute Australia, Clayton, Australia; Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, AustraliaAustralian Regenerative Medicine Institute, Monash University, Clayton, Australia; Systems Biology Institute Australia, Clayton, Australia; Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, AustraliaThe Jackson Laboratory, Bar Harbor, United StatesMurdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, AustraliaThe Jackson Laboratory, Farmington, United StatesThe Jackson Laboratory, Bar Harbor, United StatesCentre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Monash University, Clayton, AustraliaMurdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, AustraliaMurdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, AustraliaThe Jackson Laboratory, Farmington, United States; Cardiology Center, UConn Health, Farmington, United StatesThe Jackson Laboratory, Bar Harbor, United States; Australian Regenerative Medicine Institute, Monash University, Clayton, AustraliaThe Jackson Laboratory, Bar Harbor, United States; Australian Regenerative Medicine Institute, Monash University, Clayton, Australia; National Heart and Lung Institute, Imperial College London, London, United KingdomThe Jackson Laboratory, Bar Harbor, United States; Australian Regenerative Medicine Institute, Monash University, Clayton, AustraliaOrgan fibroblasts are essential components of homeostatic and diseased tissues. They participate in sculpting the extracellular matrix, sensing the microenvironment, and communicating with other resident cells. Recent studies have revealed transcriptomic heterogeneity among fibroblasts within and between organs. To dissect the basis of interorgan heterogeneity, we compare the gene expression of murine fibroblasts from different tissues (tail, skin, lung, liver, heart, kidney, and gonads) and show that they display distinct positional and organ-specific transcriptome signatures that reflect their embryonic origins. We demonstrate that expression of genes typically attributed to the surrounding parenchyma by fibroblasts is established in embryonic development and largely maintained in culture, bioengineered tissues and ectopic transplants. Targeted knockdown of key organ-specific transcription factors affects fibroblast functions, in particular genes involved in the modulation of fibrosis and inflammation. In conclusion, our data reveal that adult fibroblasts maintain an embryonic gene expression signature inherited from their organ of origin, thereby increasing our understanding of adult fibroblast heterogeneity. The knowledge of this tissue-specific gene signature may assist in targeting fibrotic diseases in a more precise, organ-specific manner.https://elifesciences.org/articles/71008fibroblastsorgan specifictranscriptomeembryonic developmentHox codeorgan identity |
| spellingShingle | Elvira Forte Mirana Ramialison Hieu T Nim Madison Mara Jacky Y Li Rachel Cohn Sandra L Daigle Sarah Boyd Edouard G Stanley Andrew G Elefanty John Travis Hinson Mauro W Costa Nadia A Rosenthal Milena B Furtado Adult mouse fibroblasts retain organ-specific transcriptomic identity eLife fibroblasts organ specific transcriptome embryonic development Hox code organ identity |
| title | Adult mouse fibroblasts retain organ-specific transcriptomic identity |
| title_full | Adult mouse fibroblasts retain organ-specific transcriptomic identity |
| title_fullStr | Adult mouse fibroblasts retain organ-specific transcriptomic identity |
| title_full_unstemmed | Adult mouse fibroblasts retain organ-specific transcriptomic identity |
| title_short | Adult mouse fibroblasts retain organ-specific transcriptomic identity |
| title_sort | adult mouse fibroblasts retain organ specific transcriptomic identity |
| topic | fibroblasts organ specific transcriptome embryonic development Hox code organ identity |
| url | https://elifesciences.org/articles/71008 |
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