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Title: Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas
Author: Mazuelas, Helena
Magallón Lorenz, Míriam
Fernández Rodríguez, Juana
Uriarte Arrazola, Itziar
Richaud Patin, Yvonne
Terribas, Ernest
Villanueva Garatachea, Alberto
Castellanos, Elisabeth
Blanco Guillermo, Ignacio
Raya Chamorro, Ángel
Chojnacki, Jakub
Heyn, Holger
Romagosa Pérez-Portabella, Cleofé
Lázaro, Conxi
Gel, Bernat
Carrió, Meritxell
Serra Arenas, Eduard
Keywords: Neurofibromatosi
Issue Date: 1-Feb-2022
Publisher: Elsevier BV
Abstract: Plexiform neurofibromas (pNFs) are developmental tumors that appear in neurofibromatosis type 1 individuals, constituting a major source of morbidity and potentially transforming into a highly metastatic sarcoma (MPNST). pNFs arise after NF1 inactivation in a cell of the neural crest (NC)-Schwann cell (SC) lineage. Here, we develop an iPSC-based NC-SC in vitro differentiation system and construct a lineage expression road map for the analysis of different 2D and 3D NF models. The best model consists of generating heterotypic spheroids (neurofibromaspheres) composed of iPSC-derived differentiating NF1((-/-)) SCs and NF1((+/-)) pNF-derived fibroblasts (Fbs). Neurofibromaspheres form by maintaining highly proliferative NF1((-/-)) cells committed to the NC-SC axis due to SC-SC and SC-Fb interactions, resulting in SC linage cells at different maturation points. Upon engraftment on the mouse sciatic nerve, neurofibromaspheres consistently generate human NF-like tumors. Analysis of expression roadmap genes in human pNF single-cell RNAseq data uncovers the presence of SC subpopulations at distinct differentiation states.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2022, vol 38, num 7
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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