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

• Main Authors: Meritxell Carrió, Helena Mazuelas, Yvonne Richaud-Patin, Bernat Gel, Ernest Terribas, Imma Rosas, Senda Jimenez-Delgado, Josep Biayna, Leen Vendredy, Ignacio Blanco, Elisabeth Castellanos, Conxi Lázaro, Ángel Raya, Eduard Serra
• Format: Article
• Language: English
• Published: Elsevier 2019-02-01
• Series: Stem Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213671119300025

Summary: 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. : In this article, Eduard Serra and colleagues describe the generation of iPSCs directly from plexiform neurofibromas (PNFs), benign Schwann cell (SC) tumors associated with neurofibromatosis type 1. iPSCs bearing the double inactivation of the NF1 gene were differentiated into SCs that exhibited a high proliferation rate, a poor myelination ability, and a tendency to form spheres, resembling PNF-derived SCs. Keywords: iPSC, neurofibromatosis type 1, plexiform neurofibroma, Schwann cell, neural crest stem cell, NF1, benign tumor