Interrogation of RDEB Epidermal Allografts after BMT Reveals Coexpression of Collagen VII and Keratin 15 with Proinflammatory Immune Cells and Fibroblasts.
Julia A Riedl, Megan Riddle, Lily Xia, Cindy Eide, Christina Boull, Christen L Ebens, Jakub Tolar
Author Information
Julia A Riedl: Medical Scientist Training Program (MD/PhD), Medical School, University of Minnesota, Minneapolis, Minnesota, USA; Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Megan Riddle: Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Lily Xia: Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Cindy Eide: Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Christina Boull: Division of Pediatric Dermatology, Department of Dermatology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Christen L Ebens: Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address: ebens012@umn.edu.
Jakub Tolar: Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by dysfunctional collagen VII protein resulting in epithelial blistering of the skin, mucosa, and gastrointestinal tract. There is no cure for RDEB, but improvement of clinical phenotype has been achieved with bone marrow transplantation and subsequent epidermal allografting from the bone marrow transplant donor. Epidermal allografting of these patients has decreased wound surface area for up to 3 years after treatment. This study aimed to determine the phenotype of the epidermal allograft cells responsible for durable persistence of wound healing and skin integrity. We found that epidermal allografts provide basal keratinocytes coexpressing collagen VII and basal stem cell marker keratin 15. Characterization of RDEB full-thickness skin biopsies with single-cell RNA sequencing uncovered proinflammatory immune and fibroblast phenotypes potentially driven by the local environment of RDEB skin. This is further highlighted by the presence of a myofibroblast population, which has not been described in healthy control human skin. Finally, we found inflammatory fibroblasts expressing profibrotic gene POSTN, which may have implications in the development of squamous cell carcinoma, a common, lethal complication of RDEB that lacks curative treatment. In conclusion, this study provides insights into and targets for future RDEB studies and treatments.
References
Nat Commun. 2021 Jun 17;12(1):3709
[PMID: 34140509]
