Document Type

Article

Publication Date

3-16-2022

Publication Title

Elife

Keywords

JMG, JGM, Animals, Fibroblasts, Fibrosis, Lung, Mice, Skin, Transcriptome

JAX Source

Elife 2022 Mar 16; 11:e71008

Volume

11

ISSN

2050-084X

PMID

35293863

DOI

https://doi.org/10.7554/elife.71008

Grant

JAX Director's Innovation Fund, GM104318, AG022308, CA034196

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 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.

Comments

We gratefully acknowledge Dr. Guoji Guo’s lab for providing the scRNAseq stromal cell dataset, and the contribution of Luis E Lima, Heidi Munger, Philipp Heinrich, and the Genome Technology, Single Cell, Light Microscopy, Flow cytometry, and Computational Sciences Services at The Jackson Laboratory for service provided.

This article is distributed under the terms of the Creative Commons Attribution License.

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