Journal: bioRxiv
Article Title: Desmoplakin mutations in cardiac fibroblasts cause TGFβ1-mediated pathological fibrogenesis in desmoplakin cardiomyopathy via beclin-1 regulation
doi: 10.1101/2024.09.09.612149
Figure Lengend Snippet: A , A simple diagram of 3 structural domains in DSP. B, All MSCs express MSC phenotypes by flow cytometry. C, An unbiased clustering analysis of global transcriptome mRNA expression profiles (a Heat map) of iPSC-MSCs, cardiac FBs, and skin FBs from the same donor (SW) by RNAseq. Increased and decreased gene expressions are shown in red and green, respectively. D-E, DSP -mutant MSCs show ≤ 50% WT DSP mRNA and DSP protein levels when compared to normal MSCs. F, All MSCs expressed similar immunostaining intensities and mRNA levels of aSMA at baseline and after TGFb1. The number of independent biological replicates for each data point is shown in all Figures. Asterisks denote p <0.05 by ANOVA except F by Kruskal-Wallis. Values are means ± SD. Scale bars are 50 µm. Raw data are in the Source Data Files for verification.
Article Snippet: To obtain a global view of how DSP deficiency affects the gene expression networks (Figures S6E-F and S7), we used Illumina mRNA expression microarrays to profile iPSC-MSCs from DSP R160X proband, DSP R160X proband’s mother (carrying the same heterozygous DSP mutation but with no clinical ACM), DSP E1159R proband, and the normal (SW) line at baseline to find common deregulated pathways.
Techniques: Flow Cytometry, Expressing, Mutagenesis, Immunostaining