Cell-lineage controlled epigenetic regulation in glioblastoma stem cells determines functionally distinct subgroups and predicts patient survival

Xi Lu, Naga Prathyusha Maturi, Malin Jarvius, Irem Yildirim, Yonglong Dang, Linxuan Zhao, Yuan Xie, E-Jean Tan, Pengwei Xing, Rolf Larsson, Mårten Fryknäs, Lene Uhrbom () and Xingqi Chen ()
Additional contact information
Xi Lu: Uppsala University
Naga Prathyusha Maturi: Uppsala University and Science for Life Laboratory, Rudbeck Laboratory
Malin Jarvius: Uppsala University and Science for Life Laboratory
Irem Yildirim: Uppsala University and Science for Life Laboratory, Rudbeck Laboratory
Yonglong Dang: Uppsala University
Linxuan Zhao: Uppsala University
Yuan Xie: Uppsala University and Science for Life Laboratory, Rudbeck Laboratory
E-Jean Tan: Uppsala University and Science for Life Laboratory, Rudbeck Laboratory
Pengwei Xing: Uppsala University
Rolf Larsson: Uppsala University and Science for Life Laboratory
Mårten Fryknäs: Uppsala University and Science for Life Laboratory
Lene Uhrbom: Uppsala University and Science for Life Laboratory, Rudbeck Laboratory
Xingqi Chen: Uppsala University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract There is ample support for developmental regulation of glioblastoma stem cells. To examine how cell lineage controls glioblastoma stem cell function, we present a cross-species epigenome analysis of mouse and human glioblastoma stem cells. We analyze and compare the chromatin-accessibility landscape of nine mouse glioblastoma stem cell cultures of three defined origins and 60 patient-derived glioblastoma stem cell cultures by assay for transposase-accessible chromatin using sequencing. This separates the mouse cultures according to cell of origin and identifies three human glioblastoma stem cell clusters that show overlapping characteristics with each of the mouse groups, and a distribution along an axis of proneural to mesenchymal phenotypes. The epigenetic-based human glioblastoma stem cell clusters display distinct functional properties and can separate patient survival. Cross-species analyses reveals conserved epigenetic regulation of mouse and human glioblastoma stem cells. We conclude that epigenetic control of glioblastoma stem cells primarily is dictated by developmental origin which impacts clinically relevant glioblastoma stem cell properties and patient survival.

Date: 2022
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DOI: 10.1038/s41467-022-29912-2

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