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 () and Jiangbing Zhou ()
Additional contact information
Jun Liu: Yale University
Xiaoying Wang: Yale University
Ann T. Chen: 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
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
W. Mark Saltzman: Yale University
Jiangbing Zhou: Yale University

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29884-3

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