Your browser doesn't support javascript.
loading
Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response.
Johnson, Kevin C; Anderson, Kevin J; Courtois, Elise T; Gujar, Amit D; Barthel, Floris P; Varn, Frederick S; Luo, Diane; Seignon, Martine; Yi, Eunhee; Kim, Hoon; Estecio, Marcos R H; Zhao, Dacheng; Tang, Ming; Navin, Nicholas E; Maurya, Rahul; Ngan, Chew Yee; Verburg, Niels; de Witt Hamer, Philip C; Bulsara, Ketan; Samuels, Michael L; Das, Sunit; Robson, Paul; Verhaak, Roel G W.
Afiliación
  • Johnson KC; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. kevin.c.johnson@jax.org.
  • Anderson KJ; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Courtois ET; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Gujar AD; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Barthel FP; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Varn FS; Department of Pathology, Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Luo D; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Seignon M; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Yi E; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Kim H; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Estecio MRH; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Zhao D; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Tang M; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Navin NE; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Maurya R; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ngan CY; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Verburg N; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • de Witt Hamer PC; Department of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Bulsara K; Department of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Samuels ML; Division of Neurosurgery, The University of Connecticut Health Center, Farmington, CT, USA.
  • Das S; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Robson P; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for SickKids, University of Toronto, Toronto, Ontario, Canada.
  • Verhaak RGW; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Nat Genet ; 53(10): 1456-1468, 2021 10.
Article en En | MEDLINE | ID: mdl-34594038
Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Neoplasias Encefálicas / Epigénesis Genética / Análisis de la Célula Individual / Plasticidad de la Célula / Glioma Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Neoplasias Encefálicas / Epigénesis Genética / Análisis de la Célula Individual / Plasticidad de la Célula / Glioma Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos