Transcriptomics,Genomics

Dataset Information

163

Pigment producing melanocytes as the cells of origin of BRAFV600E-induced mouse cutaneous melanoma


ABSTRACT: To investigate whether cutaneous melanoma originates from a resident adult melanocyte stem cell (MSC) or a mature melanocyte, we created a model that recapitulates key histopathological features of human melanomagenesis by inducing a BRafV600E-driven melanomagenic program in interfollicular (IF) melanocytes located in mouse tails. To this end, we sequenced the transcriptome of FACS-sorted individual IFE reporter-positive cells from BRaf/Pten/tdTomato mice, the tails of which had been painted with 4-HT for 31 and 72 days, respectively. These time points were chosen as melanoma cells are exclusively found in the IF epidermis at day 31 (d31) and in both epidermis and dermis at day 72 (d72). Normal IF melanocytes from Tyr::CreERT2/+; ROSA26RLSL-tdTomato/+ were also isolated and profiled These data indicated that loss of differentiation markers occurs in a subset of targeted epidermal melanoma cells before the onset of dermal invasion and that this event may, at least partly, be a consequence of induction of Zeb1 expression. Overall design: scRNAseq (SMARTseq2) of epidermal melanocytes and melanoma cells at different stages of melanomagenesis in a tail melanoma mouse model.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Sara Aibar 

PROVIDER: GSE100607 | GEO | 2017-11-16

SECONDARY ACCESSION(S): PRJNA392284

REPOSITORIES: GEO

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Publications

Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes.

Köhler Corinna C   Nittner David D   Rambow Florian F   Radaelli Enrico E   Stanchi Fabio F   Vandamme Niels N   Baggiolini Arianna A   Sommer Lukas L   Berx Geert G   van den Oord Joost J JJ   Gerhardt Holger H   Blanpain Cedric C   Marine Jean-Christophe JC  

Cell stem cell 20171012 5


To identify the cells at the origin of melanoma, we combined single-cell lineage-tracing and transcriptomics approaches with time-lapse imaging. A mouse model that recapitulates key histopathological features of human melanomagenesis was created by inducing a BRafV600E-driven melanomagenic program in tail interfollicular melanocytes. Most targeted mature, melanin-producing melanocytes expanded clonally within the epidermis before losing their differentiated features through transcriptional repro  ...[more]

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