Number of the records: 1
Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids
- 1.
SYSNO ASEP 0539639 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids Author(s) Novotný, Jiří (UMG-J) ORCID
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, ORCID
Lacina, L. (CZ)Number of authors 10 Article number 3324 Source Title Cancers (Basel). - : MDPI
Roč. 12, č. 11 (2020)Number of pages 21 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords melanoma ; spheroids ; fibroblasts ; subpopulation ; heterogeneity ; Interleukin-6 ; cytokine ; senescence-associated secretory phenotype ; extracellular matrix ; single-cell sequencing Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects LM2018131 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000592838500001 DOI 10.3390/cancers12113324 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2021 Electronic address https://www.mdpi.com/2072-6694/12/11/3324
Number of the records: 1