Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Cell stem cell | 2017

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.

Pubmed ID: 29033351 RIS Download

Mesh terms: Animals | Biomarkers | Carcinogenesis | Cell Dedifferentiation | Cell Proliferation | Dermis | Hair Follicle | Humans | Melanocytes | Melanoma | Mice | Mutation | Neoplasm Invasiveness | Proto-Oncogene Proteins B-raf | Skin Neoplasms | Skin Pigmentation | Stem Cell Niche | Tail | Transcriptome

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

View all literature mentions

Keratin 10 Polyclonal Antibody, Purified (antibody)

RRID:AB_2565049

This polyclonal antibody targets Keratin 10

View all literature mentions

S100 antibody (antibody)

RRID:AB_10013383

This polyclonal antibody targets S100 isolated from cow brain.

View all literature mentions

Phospho-Akt (Ser473) antibody (antibody)

RRID:AB_2315049

This monoclonal antibody targets Ser473

View all literature mentions

Ki-67 antibody (antibody)

RRID:AB_2335745

This monoclonal antibody targets A synthetic peptide derived from the human Ki-67 protein C-terminus

View all literature mentions

Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) antibody (antibody)

RRID:AB_2315112

This monoclonal antibody targets p44 / 42 MAPK, phospho (Thr202 / Tyr204)

View all literature mentions

ZEB1 (H-102) antibody (antibody)

RRID:AB_2217979

This polyclonal antibody targets ZEB1 (H-102)

View all literature mentions