Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas
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- dc.contributor.author Mazuelas, Helena
- dc.contributor.author Magallón-Lorenz, Míriam
- dc.contributor.author Fernández-Rodríguez, Juana
- dc.contributor.author Uriarte-Arrazola, Itziar
- dc.contributor.author Richaud Patin, Yvonne
- dc.contributor.author Terribas, Ernest
- dc.contributor.author Villanueva, Alberto
- dc.contributor.author Castellanos, Elisabeth
- dc.contributor.author Blanco, Ignacio
- dc.contributor.author Raya Chamorro, Ángel
- dc.contributor.author Chojnacki, Jakub
- dc.contributor.author Heyn, Holger
- dc.contributor.author Romagosa, Cleofé
- dc.contributor.author Lázaro García, Conxi
- dc.contributor.author Gel, Bernat
- dc.contributor.author Carrió, Meritxell
- dc.contributor.author Serra, Eduard
- dc.date.accessioned 2022-03-29T06:40:58Z
- dc.date.available 2022-03-29T06:40:58Z
- dc.date.issued 2022
- dc.description.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 roadmap 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 RNA-seq data uncovers the presence of SC subpopulations at distinct differentiation states.
- dc.format.mimetype application/pdf
- dc.identifier.citation Mazuelas H, Magallón-Lorenz M, Fernández-Rodríguez J, Uriarte-Arrazola I, Richaud-Patin Y, Terribas E, Villanueva A, Castellanos E, Blanco I, Raya Á, Chojnacki J, Heyn H, Romagosa C, Lázaro C, Gel B, Carrió M, Serra E. Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas. Cell Rep. 2022 Feb 15;38(7):110385. DOI: 10.1016/j.celrep.2022.110385
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2022.110385
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/52786
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2022 Feb 15;38(7):110385
- dc.rights © 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword RNA-seq
- dc.subject.keyword Schwann cell
- dc.subject.keyword Engraftment
- dc.subject.keyword Fibroblast
- dc.subject.keyword iPSC
- dc.subject.keyword Neural crest
- dc.subject.keyword Neurofibromatosis type 1
- dc.subject.keyword Plexiformneurofibroma
- dc.subject.keyword scRNA-seq
- dc.subject.keyword Spheroids
- dc.title Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion