Adult mouse fibroblasts retain organ-specific transcriptomic identity
- Jackson Laboratory, United States
- Monash University, Australia
- Murdoch Children's Research Institute, Australia
Abstract
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 inter-organ heterogeneity, we compare the gene expression of murine fibroblasts from different tissues (tail, skin, lung, liver, heart, kidney, 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.
Data availability
All data has been made available through public databases, as per statement in main manuscript
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Transcriptional profile of organ fibroblasts from adult miceNCBI Gene Expression Omnibus,GSE98783.
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Tissue fibroblasts conserve an organ molecular identitySequence Read Archive, SRR5590304.
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Mapping Mouse Cell Atlas by Microwell seqNCBI Gene Expression Omnibus,GSE108097.
Article and author information
Author details
Funding
Australian Research Council
- Nadia A Rosenthal
National Health and Medical Research Council
- Mirana Ramialison
- Mauro W Costa
- Nadia A Rosenthal
Heart Foundation
- Mirana Ramialison
Jackson Laboratory
- Nadia A Rosenthal
National Institutes of Health
- Nadia A Rosenthal
Leducq Foundation for Cardiovascular Research
- Nadia A Rosenthal
Australian Government
- Nadia A Rosenthal
State Government of Victoria
- Nadia A Rosenthal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#16010) of the Jackson Laboratory. All surgery was performed under tribromoethanol anesthesia, and every effort was made to minimize pain and suffering.
Human subjects: Human samples were obtained through the Sydney Heart Bank (SHB) in Australia. Investigators have not collected patient samples or been privy to patient records.
Reviewing Editor
- Paul W Noble, Cedars-Sinai Medical Centre, United States
Version history
- Preprint posted: June 4, 2021 (view preprint)
- Received: June 4, 2021
- Accepted: March 15, 2022
- Accepted Manuscript published: March 16, 2022 (version 1)
- Version of Record published: March 28, 2022 (version 2)
Copyright
© 2022, Forte et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Adult mouse fibroblasts retain organ-specific transcriptomic identity
eLife 11:e71008.
https://doi.org/10.7554/eLife.71008
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