title: Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  High-throughput cell surface and intracellular profiling of cardiac and tail fibroblasts identified canonical mesenchymal stem cell and a surprising number of cardiogenic genes, some expressed at higher levels than in whole heart. While genetically marked fibroblasts contributed heterogeneously to interstitial but not cardiomyocyte compartments in infarcted hearts, fibroblast-restricted depletion of one highly expressed cardiogenic marker, T-box 20, caused marked myocardial dysmorphology and perturbations in scar formation on myocardial infarction.
  
  
  CONCLUSIONS
  The surprising transcriptional identity of cardiac fibroblasts, the adoption of cardiogenic gene programs, and direct contribution to cardiac development and repair provoke alternative interpretations for studies on more specialized cardiac progenitors, offering a novel perspective for reinterpreting cardiac regenerative therapies.
authors.affiliation: From the Australian Regenerative Medicine Institute (M.B.F., M.W.C., E.A.P., E.S., A.R.P., A.C., N.A.R.), Department of Anatomy and Developmental Biology (A.R.P., R.B.), and Monash Biomedical Imaging (J.P.), Monash University, Melbourne, Victoria, Australia; Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.T.L., D.M.K.); Department of Pediatrics, Indiana University School of Medicine, Indianapolis (P.S., S.J.C.); and Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia (R.P.H.).
authors.forename: Milena B
authors.initials: MB
authors.lastname: Furtado
authors.forename: Mauro W
authors.initials: MW
authors.lastname: Costa
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pranoto
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Salimova
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pinto
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Lam
authors.forename: Anthony
authors.initials: A
authors.lastname: Park
authors.forename: Paige
authors.initials: P
authors.lastname: Snider
authors.forename: Anjana
authors.initials: A
authors.lastname: Chandran
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Richard
authors.initials: R
authors.lastname: Boyd
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: James
authors.initials: J
authors.lastname: Pearson
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D022661:RNA, Untranslated / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: D015415:Biomarkers; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D022661:RNA, Untranslated; D020825:T-Box Domain Proteins; C486013:Tbx20 protein, mouse; D049452:Green Fluorescent Proteins
keywords: cardiac fibroblasts; gene regulatory networks; heart; transcription factors