Abstract

Even with recent advances in lineage tracing and multiomics analyses, it is difficult to specifically identify and target heterogeneous fibroblast populations in an organ-specific manner. This study combined robust multi-organ in vitro, in vivo, and high-throughput gene expression analyses of mouse fibroblast populations derived from various organs to define organ-specific transcriptional signatures. The analyses revealed that fibroblasts derived from different organs retain transcriptional embryonic gene signatures as organ-of-origin identifiers in adulthood. Moreover, organ-specific transcriptome identities of fibroblast populations were maintained in fibroblast co-cultures in vitro and ectopic transplants in vivo. These studies advance our current understanding of the heterogeneity of fibroblast populations and suggest opportunities for their exploitation and targetability in an organ-specific manner.

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