Signatures of Dermal Fibroblasts from RDEB Pediatric Patients.


Beilin AK(1)(2), Evtushenko NA(1), Lukyanov DK(3)(4), Murashkin NN(5)(6), Ambarchian ET(5)(6), Pushkov AA(5), Savostyanov KV(5), Fisenko AP(5), Rogovaya OS(2), Vasiliev AV(2), Vorotelyak EA(2), Gurskaya NG(1)(2).
Author information:
(1)Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, 117997 Moscow, Russia.
(2)Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 26 Vavilova Str., 119334 Moscow, Russia.
(3)Center of Life Sciences, Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Building 1, 121205 Moscow, Russia.
(4)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
(5)National Medical Research Center for Children's Health, Federal State Autonomous Institution of the Ministry of Health of the Russian Federation, Lomonosovsky Prospekt, 2, Building 1, 119296 Moscow, Russia.
(6)Diagnostic and Treatment Department, University Children's Hospital
(UCH), Sechenov First Moscow State Medical University
(Sechenov University), 119435 Moscow, Russia.


The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.