gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Electrical signaling is essential for dynamic transcriptional plasticity in Glioblastoma

Elektrische Signalübertragung ist für die dynamische Transkriptionsplastizität bei Glioblastomen von wesentlicher Bedeutung

Meeting Abstract

  • presenting/speaker Kevin Joseph - Universitätsklinikum Freiburg, Translational neuroOncology Research Group, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Lea Vollmer - Universitätsklinikum Freiburg, Translational neuroOncology Research Group, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Vidhya Madapusi Ravi - Universitätsklinikum Freiburg, Translational neuroOncology Research Group, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Jürgen Beck - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Ulrich Hofmann - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Neuroelectronic Systems, Freiburg i. Br., Deutschland
  • Oliver Schnell - Universitätsklinikum Freiburg, Translational neuroOncology Research Group, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Dieter Henrik Heiland - Universitätsklinikum Freiburg, Translational neuroOncology Research Group, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV146

doi: 10.3205/22dgnc144, urn:nbn:de:0183-22dgnc1448

Published: May 25, 2022

© 2022 Joseph et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Owing to recent advances in understanding of the active functional states exhibited within glioblastoma (GBM), intra-tumoral cellular signaling has moved into focus of neuro-oncological research. In our study, we aim to explore the role of transcellular electrical signaling and investigate correlations to transcriptional dynamics and cellular behavior.

Methods: Electrophysiological characterization was carried out using 2D planar microelectrodes, in a human neocortical tissue based GBM model. Exposure to conditions such as hypoxia and acidic environment was carried out to identify signaling patterns as a response to specific environmental conditions. Effect of signaling inhibition was transcriptionally characterized by means of scRNA-sequencing with CRISPR based perturbation.

Results: Electrophysiological characterization revealed network activity exhibiting characteristics of scale-free networks. Cellular signaling was directly correlated to changes in the environment, like hypoxia or glutamatergic activation, with modulation of either frequency or amplitude of recorded events encoding information regarding changes in the local microenvironment. CRISPR based perturbation of synapse forming genes resulted in alterations in cellular morphology (p?<?0.001) and decreased cellular connectivity (p?<?0.001), with electrical signaling being significantly attenuated (p?<?0.0001). Single-cell sequencing of perturbed tumor cells in the neocortical GBM model revealed a loss of developmental lineages (FDR<0.01) and significant reduction of cellular stress response state (FDR<0.01).

Conclusion: Our findings highlight the role of electrical signaling in glioblastoma. Cellular stressors induce intercellular signaling, leading to transcriptional adaptation suggesting that there exists a highly complex and powerful mechanism for dynamic transcriptional state adaptation.