ZNF117 regulates glioblastoma stem cell differentiation towards oligodendroglial lineage

Jun Liu, Xiaoying Wang, Ann T. Chen, Xingchun Gao, Benjamin T. Himes, Hongyi Zhang, Zeming Chen, Jianhui Wang, Wendy C. Sheu, Gang Deng, Yang Xiao, Pan Zou, Shenqi Zhang, Fuyao Liu, Yong Zhu, Rong Fan, Toral R. Patel, W. Mark Saltzman, Jiangbing Zhou

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved treatment of GBM can be achieved by eliminating GSCs through inducing their differentiation. Prior efforts have been focused on studying GSC differentiation towards the astroglial lineage. However, regulation of GSC differentiation towards the neuronal and oligodendroglial lineages is largely unknown. To identify genes that control GSC differentiation to all three lineages, we performed an image-based genome-wide RNAi screen, in combination with single-cell RNA sequencing, and identified ZNF117 as a major regulator of GSC differentiation. Using patient-derived GSC cultures, we show that ZNF117 controls GSC differentiation towards the oligodendroglial lineage via the Notch pathway. We demonstrate that ZNF117 is a promising target for GSC differentiation therapy through targeted delivery of CRISPR/Cas9 gene-editing nanoparticles. Our study suggests a direction to improve GBM treatment through differentiation of GSCs towards various lineages.

Original languageEnglish (US)
Article number2196
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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