Reprogramming and Differentiation of Cutaneous Squamous Cell Carcinoma Cells in Recessive Dystrophic Epidermolysis Bullosa |
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Authors: | Avina Rami ukasz aczmaski Jagoda Jackw-Nowicka Joanna Jackw |
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Affiliation: | 1.Department of Dermatology, Columbia University, New York, NY 10032, USA;2.Laboratory of Genomics &Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;3.Department of General and Interventional Radiology and Neuroradiology, Wroclaw Medical University, 50-556 Wroclaw, Poland;4.St John’s Institute of Dermatology, King’s College London, Guy’s Campus, London SE1 9RT, UK |
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Abstract: | The early onset and rapid progression of cutaneous squamous cell carcinoma (cSCC) leads to high mortality rates in individuals with recessive dystrophic epidermolysis bullosa (RDEB). Currently, the molecular mechanisms underlying cSCC development in RDEB are not well understood and there are limited therapeutic options. RDEB-cSCC arises through the accumulation of genetic mutations; however, previous work analyzing gene expression profiles have not been able to explain its aggressive nature. Therefore, we generated a model to study RDEB-cSCC development using cellular reprograming and re-differentiation technology. We compared RDEB-cSCC to cSCC that were first reprogrammed into induced pluripotent stem cells (RDEB-cSCC-iPSC) and then differentiated back to keratinocytes (RDEB-cSCC-iKC). The RDEB-cSCC-iKC cell population had reduced proliferative capacities in vitro and in vivo, suggesting that reprogramming and re-differentiation leads to functional changes. Finally, we performed RNA-seq analysis for RDEB-cSCC, RDEB-cSCC-iPSC, and RDEB-cSCC-iKC and identified different gene expression signatures between these cell populations. Taken together, this cell culture model offers a valuable tool to study cSCC and provides a novel way to identify potential therapeutic targets for RDEB-cSCC. |
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Keywords: | induced pluripotent stem cell technology squamous cell carcinoma recessive dystrophic epidermolysis bullosa cancer biomarkers in vitro model |
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