Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue

Dylan Scott Lykke Harwood (), Vilde Pedersen, Nicolai Schou Bager, Ane Yde Schmidt, Tobias Overlund Stannius, Aušrinė Areškevičiūtė, Knud Josefsen, Dorte Schou Nørøxe, David Scheie, Hannah Rostalski, Maya Jeje Schuang Lü, Alessio Locallo, Ulrik Lassen, Frederik Otzen Bagger, Joachim Weischenfeldt, Dieter Henrik Heiland, Kristoffer Vitting-Seerup, Signe Regner Michaelsen and Bjarne Winther Kristensen ()
Additional contact information
Dylan Scott Lykke Harwood: University of Copenhagen
Vilde Pedersen: University of Copenhagen
Nicolai Schou Bager: University of Copenhagen
Ane Yde Schmidt: Copenhagen University Hospital
Tobias Overlund Stannius: Copenhagen University Hospital
Aušrinė Areškevičiūtė: Copenhagen University Hospital
Knud Josefsen: Copenhagen University Hospital
Dorte Schou Nørøxe: Copenhagen University Hospital
David Scheie: Copenhagen University Hospital
Hannah Rostalski: University of Copenhagen
Maya Jeje Schuang Lü: University of Copenhagen
Alessio Locallo: University of Copenhagen
Ulrik Lassen: Copenhagen University Hospital
Frederik Otzen Bagger: Copenhagen University Hospital
Joachim Weischenfeldt: Copenhagen University Hospital
Dieter Henrik Heiland: Medical Center—University of Freiburg
Kristoffer Vitting-Seerup: Technical University of Denmark (DTU)
Signe Regner Michaelsen: University of Copenhagen
Bjarne Winther Kristensen: University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52167-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52167-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52167-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().