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Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids
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SYSNO ASEP 0539639 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids Tvůrce(i) Novotný, Jiří (UMG-J)
Strnadová, K. (CZ)
Dvořánková, B. (CZ)
Kocourková, Šárka (UMG-J)
Jaksa, R. (CZ)
Dundr, P. (CZ)
Pačes, Václav (UMG-J) RID
Smetana, K. (CZ)
Kolář, Michal (UMG-J) RID
Lacina, L. (CZ)Celkový počet autorů 10 Číslo článku 3324 Zdroj.dok. Cancers (Basel). - : MDPI
Roč. 12, č. 11 (2020)Poč.str. 21 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova melanoma ; spheroids ; fibroblasts ; subpopulation ; heterogeneity ; Interleukin-6 ; cytokine ; senescence-associated secretory phenotype ; extracellular matrix ; single-cell sequencing Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology CEP LM2018131 GA MŠk - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000592838500001 DOI 10.3390/cancers12113324 Anotace Heterogeneous spheroids have recently acquired a prominent position in melanoma research because they incorporate microenvironmental cues relevant for melanoma. In this study, we focused on the analysis of microenvironmental factors introduced in melanoma heterogeneous spheroids by different dermal fibroblasts. We aimed to map the fibroblast diversity resulting from previously acquired damage caused by exposure to extrinsic and intrinsic stimuli. To construct heterogeneous melanoma spheroids, we used normal dermal fibroblasts from the sun-protected skin of a juvenile donor. We compared them to the fibroblasts from the sun-exposed photodamaged skin of an adult donor. Further, we analysed the spheroids by single-cell RNA sequencing. To validate transcriptional data, we also compared the immunohistochemical analysis of heterogeneous spheroids to melanoma biopsies. We have distinguished three functional clusters in primary human fibroblasts from melanoma spheroids. These clusters differed in the expression of (a) extracellular matrix-related genes, (b) pro-inflammatory factors, and (c) TGFβ signalling superfamily. We observed a broader deregulation of gene transcription in previously photodamaged cells. We have confirmed that pro-inflammatory cytokine IL-6 significantly enhances melanoma invasion to the extracellular matrix in our model. This supports the opinion that the aspects of ageing are essential for reliable melanoma 3D modelling in vitro. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2021 Elektronická adresa https://www.mdpi.com/2072-6694/12/11/3324
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