Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas

Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disease caused by mutations in the NF1 tumor suppressor gene. Plexiform neurofibromas (PNFs) are benign Schwann cell (SC) tumors of the peripheral nerve sheath that develop through NF1 inactivation and can progress toward a malignant s...

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Detalhes bibliográficos
Autores: Carrió, Meritxell, Mazuelas, Helena, Richaud-Patin, Yvonne, Gel Moreno, Bernat, Terribas, Ernest, Rosas, Imma, Jimenez Delgado, Senda, Biayna, Josep, Vendredy, Leen, Blanco Guillermo, Ignacio, Castellanos, Elisabeth, Lázaro García, Conxi, Raya Chamorro, Ángel, Serra Arenas, Eduard
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171527
Acesso em linha:https://hdl.handle.net/2445/171527
Access Level:acceso abierto
Palavra-chave:Neurofibromatosi
Antioncogens
Neurofibromatosis
Antioncogenes
Descrição
Resumo:Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disease caused by mutations in the NF1 tumor suppressor gene. Plexiform neurofibromas (PNFs) are benign Schwann cell (SC) tumors of the peripheral nerve sheath that develop through NF1 inactivation and can progress toward a malignant soft tissue sarcoma. There is a lack of non-perishable model systems to investigate PNF development. We reprogrammed PNF-derived NF1(-/-) cells, descendants from the tumor originating cell. These NF1(-/-)-induced pluripotent stem cells (iPSCs) captured the genomic status of PNFs and were able to differentiate toward neural crest stem cells and further to SCs. iPSC-derived NF1(-/-) SCs exhibited a continuous high proliferation rate, poor myelination ability, and a tendency to form 3D spheres that expressed the same markers as their PNF-derived primary SC counterparts. They represent a valuable model to study and treat PNFs. PNF-derived iPSC lines were banked for making them available.