Cells and gene expression programs in the adult human heart

Monika Litvinukova; Carlos Talavera-Lopez; Henrike Maatz; Daniel Reichart; Catherine L. Worth; Eric L. Lindberg; Masatoshi Kanda; Krzysztof Polanski; Eirini S. Fasouli; Sara Samari; Kenny Roberts; Elizabeth Tuck; Matthias Heinig; Daniel DeLaughter; Barbara McDonough; Hiroko Wakimoto; Joshua M. Gorham; Emily Nadelmann; Krishnaa T. Mahbubani; Kourosh Saeb-Parsy; Giannino Patone; Joseph J Boyle; Hongbo Zhang; Hao Zhang; Anissa Viveiros; Gavin Oudit; Omer Bayraktar; J. G. Seidman; Christine Seidman; Michela Noseda; Norbert Hubner; Sarah A. Teichmann

Within each cell compartment we identified prototypic lineage-specific genes, differentially-expressed genes that characterized subpopulations with enrichment in particular chambers, and genes with previously unknown cardiac expression. We validated these findings using in situ smFISH with RNAscope probes ( Figure 2G FB in atrial and ventricular tissues exhibited different transcriptional profiles and subpopulations, suggesting distinct functions. We found that ECM-producing and -organising fibroblasts, while present in atria and ventricles, differed in their mode of action, as exemplified by regional-specific expression of different collagen and ECM remodelling factor genes. Together with differences in the frequency of other cell types, we suggest that region-specific FB heterogeneity is critical to support CM across varying biophysical stimuli.