TY - JOUR
T1 - Reprogramming and differentiation of cutaneous squamous cell carcinoma cells in recessive dystrophic epidermolysis bullosa
AU - Rami, Avina
AU - Łaczmański, Łukasz
AU - Jacków-Nowicka, Jagoda
AU - Jacków, Joanna
N1 - Funding Information:
Funding: This study was supported by the Epidermolysis Bullosa Research Partnership (EBRP) grant, grant number PG009514 to J.J.
Funding Information:
This study was supported by the Epidermolysis Bullosa Research Partnership (EBRP) grant, grant number PG009514 to J.J.
Publisher Copyright:
© 2020 by the authors.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Cancer
KW - In vitro model
KW - Induced pluripotent stem cell technology
KW - Recessive dystrophic epidermolysis bullosa
KW - Squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85098574305&partnerID=8YFLogxK
U2 - 10.3390/ijms22010245
DO - 10.3390/ijms22010245
M3 - Article
AN - SCOPUS:85098574305
SN - 1661-6596
VL - 22
SP - 1
EP - 14
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
M1 - 245
ER -