Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes

Item Type:	Article
Title:	Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes
Creators Name:	Köhler, C. and Nittner, D. and Rambow, F. and Radaelli, E. and Stanchi, F. and Vandamme, N. and Baggiolini, A. and Sommer, L. and Berx, G. and van den Oord, J.J. and Gerhardt, H. and Blanpain, C. and Marine, J.C.
Abstract:	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 reprogramming and eventually invading the dermis. Tumors did not form within interscales, which contain both mature and dormant amelanotic melanocytes. The hair follicle bulge, which contains melanocyte stem cells, was also refractory to melanomagenesis. These studies identify varying tumor susceptibilities within the melanocytic lineage, highlighting pigment-producing cells as the melanoma cell of origin, and indicate that regional variation in tumor predisposition is dictated by microenvironmental cues rather than intrinsic differences in cellular origin. Critically, this work provides in vivo evidence that differentiated somatic cells can be reprogrammed into cancer initiating cells.
Keywords:	Cutaneous Melanoma, Cell of Origin, Mouse Model, Lineage Tracing, Time-Lapse Imaging, Single-Cell Transcriptomics, Animals, Mice
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Elsevier / Cell Press
Volume:	21
Number:	5
Page Range:	679-693.e6
Date:	2 November 2017
Official Publication:	https://doi.org/10.1016/j.stem.2017.08.003
PubMed:	View item in PubMed

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