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

(2017) CELL STEM CELL. 21(5). p.679-693
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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
CELL RNA-SEQ, STEM-CELLS, TAIL EPIDERMIS, HAIR-FOLLICLES, EXPRESSION, CANCER, NICHE, MITF, PROGRESSION, REGULATOR

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Citation

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Chicago
Kohler, Corinna, David Nittner, Florian Rambow, Enrico Radaelli, Fabio Stanchi, Niels Vandamme, Arianna Baggiolini, et al. 2017. “Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes.” Cell Stem Cell 21 (5): 679–693.
APA
Kohler, C., Nittner, D., Rambow, F., Radaelli, E., Stanchi, F., Vandamme, N., Baggiolini, A., et al. (2017). Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes. CELL STEM CELL, 21(5), 679–693.
Vancouver
1.
Kohler C, Nittner D, Rambow F, Radaelli E, Stanchi F, Vandamme N, et al. Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes. CELL STEM CELL. 2017;21(5):679–93.
MLA
Kohler, Corinna, David Nittner, Florian Rambow, et al. “Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes.” CELL STEM CELL 21.5 (2017): 679–693. Print.
@article{8556064,
  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.},
  author       = {Kohler, Corinna and Nittner, David and Rambow, Florian and Radaelli, Enrico and Stanchi, Fabio and Vandamme, Niels and Baggiolini, Arianna and Sommer, Lukas and Berx, Geert and van den Oord, Joost J and Gerhardt, Holger and Blanpain, Cedric and Marine, Jean-Christophe},
  issn         = {1934-5909},
  journal      = {CELL STEM CELL},
  keyword      = {CELL RNA-SEQ,STEM-CELLS,TAIL EPIDERMIS,HAIR-FOLLICLES,EXPRESSION,CANCER,NICHE,MITF,PROGRESSION,REGULATOR},
  language     = {eng},
  number       = {5},
  pages        = {679--693},
  title        = {Mouse cutaneous melanoma induced by mutant BRaf arises from expansion and dedifferentiation of mature pigmented melanocytes},
  url          = {http://dx.doi.org/10.1016/j.stem.2017.08.003},
  volume       = {21},
  year         = {2017},
}

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