Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair

Milena Bastos Furtado, Mauro Da Costa, Edward Matthew Adi Pranoto, Ekaterina Salimova, Ruvantha Ignatius Alexander Pinto, Nicholas T Lam, Anthony Park, Paige Snider, Anjana Chandran, Richard P Harvey, Richard Lennox Boyd, Simon Conway, James Todd Pearson, David M Kaye, Nadia Alicia Rosenthal

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147 Citations (Scopus)


Rationale: Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment but appreciation of their contribution has suffered from incomplete characterization and lack of cell-specific markers. Objective: To generate an unbiased comparative gene expression profile of the cardiac fibroblast pool, identify and characterize the role of key genes in cardiac fibroblast function, and determine their contribution to myocardial development and regeneration. Methods and Results: High-throughput cell surface and intracellular profiling of cardiac and tail fibroblasts identified canonical MSC and a surprising number of cardiogenic genes, some expressed at higher levels than in whole heart. Whilst genetically marked fibroblasts contributed heterogeneously to interstitial but not cardiomyocyte compartments in infarcted hearts, fibroblast-restricted depletion of one highly expressed cardiogenic marker, Tbx20, caused marked myocardial dysmorphology and perturbations in scar formation upon myocardial infarction. Conclusions: The surprising transcriptional identity of cardiac fibroblasts, the adoption of cardiogenic gene programs and direct contribution to cardiac development and repair provokes alternative interpretations for studies on more specialized cardiac progenitors, offering a novel perspective for reinterpreting cardiac regenerative therapies.
Original languageEnglish
Pages (from-to)1422 - 1434
Number of pages13
JournalCirculation Research
Issue number9
Publication statusPublished - 2014

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