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Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

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    SYSNO ASEP0539639
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleSingle-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids
    Author(s) 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)
    Number of authors10
    Article number3324
    Source TitleCancers (Basel). - : MDPI
    Roč. 12, č. 11 (2020)
    Number of pages21 s.
    Publication formOnline - E
    Languageeng - English
    CountryCH - Switzerland
    Keywordsmelanoma ; spheroids ; fibroblasts ; subpopulation ; heterogeneity ; Interleukin-6 ; cytokine ; senescence-associated secretory phenotype ; extracellular matrix ; single-cell sequencing
    Subject RIVEB - Genetics ; Molecular Biology
    OECD categoryBiochemistry and molecular biology
    R&D ProjectsLM2018131 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingOpen access
    Institutional supportUMG-J - RVO:68378050
    UT WOS000592838500001
    DOI10.3390/cancers12113324
    AnnotationHeterogeneous 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.
    WorkplaceInstitute of Molecular Genetics
    ContactGabriela Marešová, maresova@img.cas.cz, Tel.: 241 063 217
    Year of Publishing2021
    Electronic addresshttps://www.mdpi.com/2072-6694/12/11/3324
Number of the records: 1