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ZNF117 regulates glioblastoma stem cell differentiation towards oligodendroglial lineage

Author

Listed:
  • Jun Liu

    (Yale University)

  • Xiaoying Wang

    (Yale University
    Jiangnan University)

  • Ann T. Chen

    (Yale University
    Yale University)

  • Xingchun Gao

    (Yale University)

  • Benjamin T. Himes

    (Yale University)

  • Hongyi Zhang

    (Yale University)

  • Zeming Chen

    (Yale University)

  • Jianhui Wang

    (Yale University)

  • Wendy C. Sheu

    (Yale University
    Yale University)

  • Gang Deng

    (Yale University)

  • Yang Xiao

    (Yale University)

  • Pan Zou

    (Yale University)

  • Shenqi Zhang

    (Yale University)

  • Fuyao Liu

    (Yale University)

  • Yong Zhu

    (Yale University)

  • Rong Fan

    (Yale University)

  • Toral R. Patel

    (Yale University
    University of Texas Southwestern Medical Center)

  • W. Mark Saltzman

    (Yale University)

  • Jiangbing Zhou

    (Yale University
    Yale University)

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.

Suggested Citation

  • 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, 2022. "ZNF117 regulates glioblastoma stem cell differentiation towards oligodendroglial lineage," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29884-3
    DOI: 10.1038/s41467-022-29884-3
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    References listed on IDEAS

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