Reprogramming and differentiation of cutaneous squamous cell carcinoma cells in recessive dystrophic epidermolysis bullosa

Avina Rami, Łukasz Łaczmański, Jagoda Jacków-Nowicka, Joanna Jacków*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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). Cur-rently, 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 prolifera-tive 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.

Original languageEnglish
Article number245
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume22
Issue number1
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • Biomarkers
  • Cancer
  • In vitro model
  • Induced pluripotent stem cell technology
  • Recessive dystrophic epidermolysis bullosa
  • Squamous cell carcinoma

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