EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA

Journal article

Ilon Liu, Jiang Li, Erik R Samuelsson, Sergio Marco Salas, A. Beck, Olivia A Hack, Daeun Jeong, McKenzie L Shaw, B. Englinger, Jenna LaBelle, Hafsa M Mire, S. Madlener, Lisa Mayr, Michael A Quezada, Maria C Trissal, E. Panditharatna, K. Ernst, Taylor A. Gatesman, Matthew J Halbert, Hana Pálová, P. Pokorná, J. Štěrba, O. Slabý, R. Geyeregger, A. Diaz, A. Resnick, M. Suvà, David Jones, S. Agnihotri, Jessica Ostlin, C. Koschmann, C. Haberler, T. Czech, I. Slavc, J. Cotter, K. Ligon, S. Alexandrescu, W. Yung, I. Arrillaga-Romany, J. Gojo, M. Monje, M. Nilsson, Mariella G. Filbin
Neuro-Oncology, 2022

Semantic Scholar DOI

Cite

APA Click to copy
Liu, I., Li, J., Samuelsson, E. R., Salas, S. M., Beck, A., Hack, O. A., … Filbin, M. G. (2022). EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA. Neuro-Oncology.

Chicago/Turabian Click to copy
Liu, Ilon, Jiang Li, Erik R Samuelsson, Sergio Marco Salas, A. Beck, Olivia A Hack, Daeun Jeong, et al. “EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA.” Neuro-Oncology (2022).

MLA Click to copy
Liu, Ilon, et al. “EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA.” Neuro-Oncology, 2022.

BibTeX Click to copy

@article{ilon2022a,
  title = {EPCO-21. THE SPATIAL ORGANIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA},
  year = {2022},
  journal = {Neuro-Oncology},
  author = {Liu, Ilon and Li, Jiang and Samuelsson, Erik R and Salas, Sergio Marco and Beck, A. and Hack, Olivia A and Jeong, Daeun and Shaw, McKenzie L and Englinger, B. and LaBelle, Jenna and Mire, Hafsa M and Madlener, S. and Mayr, Lisa and Quezada, Michael A and Trissal, Maria C and Panditharatna, E. and Ernst, K. and Gatesman, Taylor A. and Halbert, Matthew J and Pálová, Hana and Pokorná, P. and Štěrba, J. and Slabý, O. and Geyeregger, R. and Diaz, A. and Resnick, A. and Suvà, M. and Jones, David and Agnihotri, S. and Ostlin, Jessica and Koschmann, C. and Haberler, C. and Czech, T. and Slavc, I. and Cotter, J. and Ligon, K. and Alexandrescu, S. and Yung, W. and Arrillaga-Romany, I. and Gojo, J. and Monje, M. and Nilsson, M. and Filbin, Mariella G.}
}

Abstract

Histone 3 lysine27-to-methionine mutant diffuse midline gliomas (H3-K27M DMGs) are among the most lethal brain tumors. Their putative cellular hierarchy has been shown to be driven by self-renewing stem-like cells arrested in an oligodendrocyte precursor-like (OPC-like) state, of which few cells are able to differentiate towards more mature astrocyte (AC)-like and oligodendrocyte (OC)-like cells. However, the spatial organization underlying this tumor cell architecture and its microenvironmental interactions in intact H3-K27M DMG tissues remain unknown. Here, we profiled the single cell transcriptomes of 45 patient H3-K27M DMGs and derived cell population-specific marker gene combinations to characterize the single cell spatial organization of 16 tumors using targeted in situ sequencing. We thereby resolved different malignant and non-malignant cell populations including cycling, OPC-like, AC-like, OC-like, mesenchymal tumor cells, and non-malignant oligodendrocytes, astrocytes, neurons, myeloid cells, T cells, and vascular cells directly in situ. Global neighborhood analyses indicate a higher tendency of cycling OPC-like cells, vascular cells, and neurons to localize within a more restricted homogeneous compartment, whereas AC-like cells, non-malignant astrocytes and myeloid cells tend to intermingle with different cell populations in a more diffuse manner. Among malignant cells, we observed cycling OPC-like and OC-like cells to co-localize within a niche-like structure that is surrounded by more differentiated AC-like cells. We further validated this stem-like niche at the protein level using multiplexed immunofluorescence via the CODEX system. Finally, we characterized relationships between malignant and non-malignant cells, consistently identifying preferred neighborhoods of mesenchymal tumor cells with vascular and myeloid cells. Together, this study resolves the spatial architecture of H3-K27M DMG malignant and non-malignant cells at single cell resolution and identifies a local niche of the oligodendroglial lineage containing the OPC-like cancer stem-like cells, thus providing novel insights into the cancer stem-like compartment in H3-K27M DMGs and suggesting potential avenues for its perturbation.