ArticleProceedings of the National Academy of Sciences of the United States of America2015
In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Neurofibromatosis Type 1 and MEK Inhibition: A Comprehensive Review with Focus on Selumetinib Therapy.Journal of clinical medicine · 2025Review
- Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells.Cancer research communications · 2025Article
- Generation of heterozygous and homozygous NF1 lines from human-induced pluripotent stem cells using CRISPR/Cas9 to investigate bone defects associated with neurofibromatosis type 1.Frontiers in cell and developmental biology · 2024Article
- Periampullary tumors in a patient with pancreatic divisum and neurofibromatosis type 1: a case report.Hereditary cancer in clinical practice · 2023Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Skeletal Muscle Cells Derived from Induced Pluripotent Stem Cells: A Platform for Limb Girdle Muscular Dystrophies.Biomedicines · 2022Article
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- Severe Phenotype in Patients with Large Deletions ofCancers · 2021Article
- Targeted Therapy in Melanoma and Mechanisms of Resistance.International journal of molecular sciences · 2020Review
- Neurofibromin 1 expression is negatively correlated with malignancy and prognosis of epithelial ovarian cancer.International journal of clinical and experimental pathology · 2019Article
- Increased extracellular matrix deposition during chondrogenic differentiation of dental pulp stem cells from individuals with neurofibromatosis type 1: an in vitro 2D and 3D study.Orphanet journal of rare diseases · 2018Article
- Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes.Scientific reports · 2018Article
- The NF1 gene in tumor syndromes and melanoma.Laboratory investigation; a journal of technical methods and pathology · 2017Review
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
Corrections and comments
- Commented on byWhat's up NF1?2016
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
"Café-au-lait" macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.
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