{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:30:14Z","timestamp":1793766614908,"version":"4.6.1"},"reference-count":163,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 1200885"],"award-info":[{"award-number":["FONDECYT 1200885"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 1211613"],"award-info":[{"award-number":["FONDECYT 1211613"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 3180621"],"award-info":[{"award-number":["FONDECYT 3180621"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["National PhD 21150719"],"award-info":[{"award-number":["National PhD 21150719"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["National PhD 21181983"],"award-info":[{"award-number":["National PhD 21181983"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Juan de la Cierva Grant","award":["FJCI-2017-32865"],"award-info":[{"award-number":["FJCI-2017-32865"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Glioblastoma (GBM) is the most frequent and aggressive brain tumor, characterized by great resistance to treatments, as well as inter- and intra-tumoral heterogeneity. GBM exhibits infiltration, vascularization and hypoxia-associated necrosis, characteristics that shape a unique microenvironment in which diverse cell types are integrated. A subpopulation of cells denominated GBM stem-like cells (GSCs) exhibits multipotency and self-renewal capacity. GSCs are considered the conductors of tumor progression due to their high tumorigenic capacity, enhanced proliferation, invasion and therapeutic resistance compared to non-GSCs cells. GSCs have been classified into two molecular subtypes: proneural and mesenchymal, the latter showing a more aggressive phenotype. Tumor microenvironment and therapy can induce a proneural-to-mesenchymal transition, as a mechanism of adaptation and resistance to treatments. In addition, GSCs can transition between quiescent and proliferative substates, allowing them to persist in different niches and adapt to different stages of tumor progression. Three niches have been described for GSCs: hypoxic\/necrotic, invasive and perivascular, enhancing metabolic changes and cellular interactions shaping GSCs phenotype through metabolic changes and cellular interactions that favor their stemness. The phenotypic flexibility of GSCs to adapt to each niche is modulated by dynamic epigenetic modifications. Methylases, demethylases and histone deacetylase are deregulated in GSCs, allowing them to unlock transcriptional programs that are necessary for cell survival and plasticity. In this review, we described the effects of GSCs plasticity on GBM progression, discussing the role of GSCs niches on modulating their phenotype. Finally, we described epigenetic alterations in GSCs that are important for stemness, cell fate and therapeutic resistance.<\/jats:p>","DOI":"10.3390\/biology11020313","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Adapt to Persist: Glioblastoma Microenvironment and Epigenetic Regulation on Cell Plasticity"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2148-7279","authenticated-orcid":false,"given":"Daniel","family":"Uribe","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-8698","authenticated-orcid":false,"given":"Ignacio","family":"Niechi","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6561-6357","authenticated-orcid":false,"given":"Gorjana","family":"Rackov","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda-Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 I.","family":"Erices","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rody","family":"San Mart\u00edn","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Quezada","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Minniti, G., Lombardi, G., and Paolini, S. 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