2026-08-29T09:10:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/234432024-11-28T19:30:46Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud
author
Sesé, Borja
author
Íñiguez-Muñoz, Sandra
author
Ensenyat-Mendez, Miquel
author
Llinàs-Arias, Pere
author
Ramis, Guillem
author
Orozco, Javier IJ
author
Fernandez de Mattos, Silvia
author
Villalonga, Priam
author
Marzese, Diego M
2024-10-04T13:22:52Z
2024-10-04T13:22:52Z
2022-04-21
Sesé B, Íñiguez-Muñoz S, Ensenyat-Mendez M, Llinàs-Arias P, Ramis G, Orozco JIJ, et al. Glioblastoma Embryonic-like Stem Cells Exhibit Immune-Evasive Phenotype. Cancers. 2022 Apr 21;14(9):2070.
10.3390/cancers14092070
2072-6694
Cancers
http://hdl.handle.net/20.500.13003/18081
35565200
L2016459413
2-s2.0-85128514285
https://hdl.handle.net/20.500.12105/23443
794542400001
Glioma stem cells (GSCs) have self-renewal and tumor-initiating capacities involved in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Core-GSCs (c-GSCs) were identified by selecting cells co-expressing high levels of embryonic stem cell (ESC) markers from a single-cell RNA-seq patient-derived GBM dataset (n = 28). Induced c-GSCs (ic-GSCs) were generated by reprogramming GBM-derived cells (GBM-DCs) using induced pluripotent stem cell (iPSC) technology. The characterization of ic-GSCs and GBM-DCs was conducted by immunostaining, transcriptomic, and DNA methylation (DNAm) analysis. We identified a GSC population (4.22% ﾱ 0.59) exhibiting concurrent high expression of ESC markers and downregulation of immune-associated pathways, named c-GSCs. In vitro ic-GSCs presented high expression of ESC markers and downregulation of antigen presentation HLA proteins. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (? = 0.71). Integration of our epigenomic profiling with 833 functional ENCODE epigenetic maps identifies increased DNA methylation on HLA genes' regulatory regions associated with polycomb repressive marks in a stem-like phenotype. This study unravels glioblastoma immune-evasive mechanisms involving a c-GSC population. In addition, it provides a cellular model with paired gene expression, and DNA methylation maps to explore potential therapeutic complements for GBM immunotherapy.
eng
Glioblastoma Embryonic-like Stem Cells Exhibit Immune-Evasive Phenotype
research article