Adult mouse fibroblasts retain organ-specific transcriptomic identity

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

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere71008
Number of pages26
JournaleLife
Volume11
DOIs
Publication statusPublished - 16 Mar 2022

Keywords

  • cell biology
  • developmental biology
  • embryonic development
  • fibroblasts
  • Hox code
  • mouse
  • organ identity
  • organ specific
  • transcriptome

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