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P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells.
Muthukrishnan, Sree Deepthi; Kawaguchi, Riki; Nair, Pooja; Prasad, Rachna; Qin, Yue; Johnson, Maverick; Wang, Qing; VanderVeer-Harris, Nathan; Pham, Amy; Alvarado, Alvaro G; Condro, Michael C; Gao, Fuying; Gau, Raymond; Castro, Maria G; Lowenstein, Pedro R; Deb, Arjun; Hinman, Jason D; Pajonk, Frank; Burns, Terry C; Goldman, Steven A; Geschwind, Daniel H; Kornblum, Harley I.
Affiliation
  • Muthukrishnan SD; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Kawaguchi R; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Nair P; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Prasad R; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Qin Y; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Johnson M; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Wang Q; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • VanderVeer-Harris N; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Pham A; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Alvarado AG; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Condro MC; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Gao F; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Gau R; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Castro MG; Department of Neurosurgery, and Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Lowenstein PR; Department of Neurosurgery, and Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Deb A; Division of Cardiology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Hinman JD; Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Pajonk F; Department of Radiation Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Burns TC; Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA.
  • Goldman SA; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA.
  • Geschwind DH; Center for Translational Neuromedicine, University of Coppenhagen School of Medicine, Coppenhagen, Denmark.
  • Kornblum HI; The UCLA Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Nat Commun ; 13(1): 6202, 2022 10 19.
Article in En | MEDLINE | ID: mdl-36261421
ABSTRACT
Glioma stem cells (GSC) exhibit plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. Here, we employ single-cell and whole transcriptomic analyses to uncover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular genes allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation and inhibits the adaptive conversion of GSC into vascular-like cells and tumor growth. Our findings highlight a role for P300 in radiation-induced stress response, suggesting a therapeutic approach to prevent glioma recurrence.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioma / Neoplasm Recurrence, Local Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioma / Neoplasm Recurrence, Local Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States