Transcriptomic effect of Fbn1 G234D/G234D mutation on neonatal skin fibroblast

This study contains RNA-seq analysis of neonatal dermal fibroblasts from mice with Fbn1 G234D/G234D mutation to uncover its impact on ECM gene expression, potentially shedding light on the tight skin phenotype. While both wild-type (WT) and mutant fibroblasts showed differences, two of the mutants exhibited more significant changes, aligning with the early onset of the disease. These earlier data was deposited in GSE268383. In this study we added 2 more wild type fibroblasts and 3 more homozygous mutant cells to ascertain the features we obtained prevously. As previously noted, there was no obvious change in ECM and ECM-modifying genes, such as the LOX family, Fbn1, and TGFβ/BMP signaling genes; while the mutants displayed upregulation of muscle developmental genes (e.g., Myod1, Myog, Myh family), immune response, and cell-cell adhesion/cytoskeletal genes. In line with previous data, downregulated genes were still enriched for histone genes and developmental transcription factors, hinting at potential chromatin/transcriptional state modifications underlying the tight skin phenotype. These transcriptomic findings underscore the need for further investigation into the mechanobiological implications of Fbn1G234D/G234D fibroblasts. To investigate whether the mutation induces intrinsic changes in fibroblasts that result in alterations in ECM gene expression, RNA sequencing (RNA-seq) was conducted on primary cultures of neonatal fibroblasts collected from the dermis of 4 WT and 4 mutant mice, and on additional primary cultures of neonatal fibroblasts collected from the dermis of 2 WT and 3 mutant mice