Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas
| العنوان: | Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas |
|---|---|
| المؤلفون: | Helena Mazuelas, Imma Rosas, Meritxell Carrió, Ernest Terribas, Angel Raya, Eduard Serra, Josep Biayna, Ignacio Blanco, Yvonne Richaud-Patin, Senda Jiménez-Delgado, Bernat Gel, Conxi Lázaro, Leen Vendredy, Elisabeth Castellanos |
| المصدر: | Dipòsit Digital de la UB Universidad de Barcelona Stem Cell Reports Stem Cell Reports, Vol 12, Iss 2, Pp 411-426 (2019) r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| بيانات النشر: | Cell Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, neural crest stem cell, Carcinogenesis, plexiform neurofibroma, neurofibromatosis type 1, Biochemistry, 0302 clinical medicine, benign tumor, Genes, Tumor Suppressor, Child, Induced pluripotent stem cell, lcsh:QH301-705.5, lcsh:R5-920, iPSC, Neural crest, Middle Aged, Cellular Reprogramming, Schwann cell, medicine.anatomical_structure, Neural Crest, Female, Stem cell, Antioncogenes, lcsh:Medicine (General), Reprogramming, Adult, Resource, congenital, hereditary, and neonatal diseases and abnormalities, Neurofibromatosis 1, Adolescent, Genotype, Tumor suppressor gene, Biology, Neurofibromatosis, Young Adult, 03 medical and health sciences, Plexiform neurofibroma, Genetics, medicine, Humans, Genetic Predisposition to Disease, neoplasms, Aged, Cell Proliferation, Neurofibroma, Plexiform, Neurofibromatosi, Correction, Cell Biology, medicine.disease, Antioncogens, 030104 developmental biology, nervous system, lcsh:Biology (General), NF1, Mutation, Cancer research, Schwann Cells, Human medicine, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology |
| الوصف: | 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. Graphical Abstract Highlights • We generated iPSCs from neurofibromatosis type 1 plexiform neurofibroma (PNF) cells • PNF-derived iPSCs were differentiated into neural crest and Schwann cells (SCs) • iPSC-differentiated NF1(−/−) SCs exhibit a high proliferation rate and form spheres • Sphere-forming SCs express the same markers as their primary PNF counterparts 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. |
| وصف الملف: | application/pdf; pdf |
| تدمد: | 2213-6711 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8acd1bc377c36981a7b04aa2bebe7987Test http://hdl.handle.net/2445/171527Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8acd1bc377c36981a7b04aa2bebe7987 |
| قاعدة البيانات: | OpenAIRE |
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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.<br />Graphical Abstract<br />Highlights • We generated iPSCs from neurofibromatosis type 1 plexiform neurofibroma (PNF) cells • PNF-derived iPSCs were differentiated into neural crest and Schwann cells (SCs) • iPSC-differentiated NF1(−/−) SCs exhibit a high proliferation rate and form spheres • Sphere-forming SCs express the same markers as their primary PNF counterparts<br />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. ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => application/pdf; pdf ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 2213-6711 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8acd1bc377c36981a7b04aa2bebe7987" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8acd1bc377c36981a7b04aa2bebe7987</link><br /><link linkTarget="URL" linkTerm="http://hdl.handle.net/2445/171527" linkWindow="_blank">http://hdl.handle.net/2445/171527</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....8acd1bc377c36981a7b04aa2bebe7987 ) |
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