Project abstract for group tolarj

Single-Cell RNA-seq of Skin Cells From RDEB Patients

Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating skin disease caused by functional mutations in the COL7A1 gene coding for type VII collagen (C7), the major component of anchoring fibrils that attach the dermis to the epidermis. Lack of C7 causes extreme skin fragility resulting in blistering wounds covering large areas of the body. Over time, continuous wounding results in syndactyly of the fingers and toes and narrowing of the esophagus. Median survival is 30 years as patients are at high risk for malnutrition and anemia, deadly infections, and aggressive squamous cell carcinoma. This study uses RNA-seq to compare gene expression between fibroblasts from the skin of RDEB patients and their healthy siblings. Previous studies have characterized the effect of C7 depletion on C7 interacting proteins such as lamin-332 and integrinα6β4. This study goes beyond this by surveying the entire transcriptome, enabling the researchers to compare not only individual genes but also gene networks, revealing novel pathways affected by this disease. Furthermore, the researchers have used the commercially available microfluidic platform (Fluidigm C1 AutoPrep) to perform single-cell RNA-seq on fibroblasts from these same patients and their siblings. Current work involves investigating the heterogeneity of these cell populations.

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