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The study evaluates whether expressing NeuroD1 (ND1), a master neurogenesis transcription factor, in GBM cells can force differentiation toward post-mitotic neurons and suppress tumor progression. Human GBM cell lines were transduced with AAV carrying ND1, inducing neuronal markers (MAP2, TUJ1, NeuN) and reducing proliferation, migration, and tumor growth. ND1-driven transdifferentiation involved Wnt signaling, was enhanced under hypoxia, promoted apoptosis, and yielded p53 expression. In an orthotopic mouse model, ND1-reprogrammed cells formed smaller tumors and expressed neuronal markers in vivo, overcoming drug resistance.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/reprogramming-glioblastoma-cells-into-non-cancerous-neuronal-cells-as-a-novel-anti-cancer-strategy/330833/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/reprogramming-glioblastoma-cells-into-non-cancerous-neuronal-cells-as-a-novel-anti-cancer-strategy/330833.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What hypothesis does the study test about GBM cells and ND1?","Question",{"text":112,"@type":113},"The study tests whether ND1 expression in GBM cells can drive differentiation toward post-mitotic neurons and halt GBM tumor progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is ND1 delivered to GBM cells in this research?",{"text":117,"@type":113},"ND1 is delivered using an adeno-associated virus (AAV) package carrying ND1, followed by analysis of neuronal marker expression and functional changes.",{"name":119,"@type":110,"acceptedAnswer":120},"What factors regulate ND1-induced transdifferentiation and how does hypoxia affect it?",{"text":121,"@type":113},"ND1-induced transdifferentiation is regulated by Wnt signaling and is markedly enhanced under hypoxic conditions compared with normoxic conditions.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330833,1790308923,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","cells  \nArticle  \nReprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy  \nMichael Q. Jiang 1,2,†, Shan Ping Yu 1,2,3, *,†, Takira Estaba 1, Emily Choi 1, Ken Berglund 4, Xiaohuan Gu 1,2 and Ling Wei 1, *  \nCitation: Jiang, M.Q.; Yu, S.P.; Estaba, T.; Choi, E.; Berglund, K.; Gu, X.; Wei, L. Reprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy. Cells 2024, 13, 897. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells13110897](10.3390/cells13110897)  \nAcademic Editor: Javier S. Castresana  \nReceived: 11 April 2024  \nRevised: 11 May 2024  \nAccepted: 21 May 2024  \nPublished: 23 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30033, USA; [michaeljiang@emory.edu](michaeljiang@emory.edu) (M.Q.J.); [testaba@emory.edu](testaba@emory.edu) (T.E.); [emily.choi@emory.edu](emily.choi@emory.edu) (E.C.); [xiaohuan.gu@emory.edu](xiaohuan.gu@emory.edu) (X.G.)  \n2 Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA  \n3 Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30033, USA  \n4 Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA; [ken.berglund@emory.edu](ken.berglund@emory.edu)  \n* Correspondence: [spyu@emory.edu](spyu@emory.edu) (S.P.Y.); [lwei7@emory.edu](lwei7@emory.edu) (L.W.)† These authors contributed equally to this work.  \nAbstract: Glioblastoma Multiforme (GBM) is an aggressive brain tumor with a high mortality rate. Direct reprogramming of glial cells to different cell lineages, such as induced neural stem cells (iNSCs) and induced neurons (iNeurons), provides genetic tools to manipulate a cell’s fate as a potential therapy for neurological diseases. NeuroD1 (ND1) is a master transcriptional factor for neurogenesis and it promotes neuronal differentiation. In the present study, we tested the hypothesis that the expression of ND1 in GBM cells can force them to differentiate toward post-mitotic neurons and halt GBM tumor progression. In cultured human GBM cell lines, including LN229, U87, and U373 as temozolomide (TMZ)-sensitive and T98G as TMZ-resistant cells, the neuronal lineage conversion was induced by an adeno-associated virus (AAV) package carrying ND1 . Twenty-one days after AAV-ND1 transduction, ND1-expressing cells displayed neuronal markers MAP2, TUJ1, and NeuN. The ND1-induced transdifferentiation was regulated by Wnt signaling and markedly enhanced under a hypoxic condition (2% O 2 vs. 21% O2 ) . ND1-expressing GBM cultures had fewer BrdU-positive proliferating cells compared to vector control cultures. Increased cell death was visualized by TUNEL staining, and reduced migrative activity was demonstrated in the wound-healing test after ND1 reprogramming in both TMZ-sensitive and-resistant GBM cells. In a striking contrast to cancer cells, converted cells expressed the anti-tumor gene p53 . In an orthotopical GBM mouse model, AAV-ND1-reprogrammed U373 cells were transplanted into the fornix of the cyclosporine-immunocompromised C57BL/6 mouse brain. Compared to control GBM cell-formed tumors, cells from ND1-reprogrammed cultures formed smaller tumors and expressed neuronal markers such as TUJ1 in the brain. Thus, reprogramming using a single-factor ND1 overcame drug resistance, converting malignant cells of heterogeneous GBM cells to normal neuron-like cells in vitro and in vivo. These novel observations warrant further research using patient-derived GBM cells and patient-derived xe","cbCairQ33D3NpFtI","https://ap.wps.com/l/cbCairQ33D3NpFtI","pdf",10523892,21,"English","# Introduction\n## GBM background and treatment challenges\n## Therapeutic strategies and limitations\n# Abstract\n## Core hypothesis and approach\n## Experimental findings in vitro and in vivo","[{\"question\":\"What hypothesis does the study test about GBM cells and ND1?\",\"answer\":\"The study tests whether ND1 expression in GBM cells can drive differentiation toward post-mitotic neurons and halt GBM tumor progression.\"},{\"question\":\"How is ND1 delivered to GBM cells in this research?\",\"answer\":\"ND1 is delivered using an adeno-associated virus (AAV) package carrying ND1, followed by analysis of neuronal marker expression and functional changes.\"},{\"question\":\"What factors regulate ND1-induced transdifferentiation and how does hypoxia affect it?\",\"answer\":\"ND1-induced transdifferentiation is regulated by Wnt signaling and is markedly enhanced under hypoxic conditions compared with normoxic conditions.\"}]","Reprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy | PDF",1789990383,53]