ROLE OF TCF21 IN PERINATAL CARDIAC FIBROBLASTS PROLIFERATION AND GENE EXPRESSION
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2020
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Cell and Molecular Biology
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Cardiac fibroblasts play a dominant role in heart disease, but our understanding of the signals that control these cells during heart development is inadequate. Tcf21 is a coronary artery disease associated gene whose function in the heart is not well understood. Previously using Tcf21 null animals, we have demonstrated that this basic helix loop helix transcription factor is essential for the formation of epicardial-derived cardiac fibroblasts. Lack of Tcf21 resulted in a failure of cardiac fibroblast progenitor migration from the epicardium. Recently, we have found that Tcf21 continues to be expressed in mature cardiac fibroblasts suggesting a continued role for this transcription factor. To evaluate the function of Tcf21 after embryonic development, we generated animals which lacked Tcf21 in the fibroblast lineage. When Tcf21 is removed at birth, we find a 30 percent reduction in the number of fibroblasts. Using EdU, we determined that loss of Tcf21 leads to reduced fibroblast proliferation in the perinatal period. To identify transcriptional targets of Tcf21, we have compared fibroblast transcriptomes in control and Tcf21 deficient fibroblasts. We have found an increase in lipid genes in the Tcf21 deficient fibroblasts. Taken together our results demonstrate that Tcf21 continues to play important roles in fibroblast biology beyond the initial formation of cardiac fibroblasts from the epicardium.
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Molecular biology
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43 pages
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