Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts [* Cross-Reference *]

Version 1.0

Yahaya A Yabo; Pilar M. Moreno‐Sanchez; Yolanda Pires‐Afonso; Tony Kaoma; Bakhtiyor Nosirov; Andrea Scafidi; Luca Ermini; Anuja Lipsa; Anaïs Oudin; Dimitrios Kyriakis; Kamil Grzyb; Suresh Poovathingal; Aurélie Poli; Arnaud Muller; Réka Tóth; Barbara Klink; Guy Berchem; C. Berthold; Frank Hertel; Michel Mittelbronn; Dieter Henrik Heiland; Alexander Skupin; Petr V. Nazarov; Simone P. Niclou; Alessandro Michelucci; Anna Golebiewska, 2026, "Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.BM7J2B, LIST Open Repository, V1

Learn about Data Citation Standards.

Contact Owner

Dataset Metrics

0 Downloads

Description	Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. Methods: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. Results: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood–brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. Conclusions: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment. Graphical Abstract: (Figure presented.) (2024-04-02) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1186/s13073-024-01321-8 for the original and latest version of the publication* (2026-07-01)
Subject	Medicine, Health and Life Sciences
Keyword	Microglia, Tumor microenvironment, Myeloid, Glioma, Phenotype, Immune system, Brain tumor, Cancer research, Transcriptome, Biology, Population, Cell, Immunology, Medicine, Pathology, Inflammation, Gene expression, Gene, Genetics
License/Data Use Agreement	CC BY 4.0


There are no files in this dataset.

Citation Metadata

Persistent Identifier	perma:LIST.BM7J2B
Publication Date	2026-07-06
Title	Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts [* Cross-Reference *]
Other Identifier	https://doi.org/10.1186/s13073-024-01321-8 OpenAlex ID: https://openalex.org/W4393412071
Author	Yahaya A Yabo (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-1128-6038 Pilar M. Moreno‐Sanchez (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-1479-8039 Yolanda Pires‐Afonso (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-5773-414X Tony Kaoma (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-1269-4826 Bakhtiyor Nosirov (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-4644-2758 Andrea Scafidi (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3089-2439 Luca Ermini (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0001-8109-6021 Anuja Lipsa (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-9668-6048 Anaïs Oudin (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0001-5552-9823 Dimitrios Kyriakis (University of Luxembourg) - ORCID: https://orcid.org/0000-0003-1643-2310 Kamil Grzyb (University of Luxembourg) - ORCID: https://orcid.org/0000-0002-2416-9500 Suresh Poovathingal (University of Luxembourg, Vlaams Instituut voor Biotechnologie) - ORCID: https://orcid.org/0000-0002-3236-2255 Aurélie Poli (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-7986-0761 Arnaud Muller (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3841-4722 Réka Tóth (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-6096-1052 Barbara Klink (German Cancer Research Center, Heidelberg University, Luxembourg Institute of Health, National Center for Tumor Diseases, Laboratoire National de Santé, University Hospital Carl Gustav Carus, Technische Universität Dresden) - ORCID: https://orcid.org/0000-0002-8753-8238 Guy Berchem (Centre Hospitalier de Luxembourg, University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0003-0157-2257 C. Berthold (Centre Hospitalier de Luxembourg) Frank Hertel (Centre Hospitalier de Luxembourg) Michel Mittelbronn (University of Luxembourg, Luxembourg Institute of Health, Laboratoire National de Santé) - ORCID: https://orcid.org/0000-0002-2998-052X Dieter Henrik Heiland (Northwestern University, University of Freiburg, German Cancer Research Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Medical Center Freiburg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, Neurological Surgery) - ORCID: https://orcid.org/0000-0002-9258-3033 Alexander Skupin (University of Luxembourg, University of California San Diego, Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0002-8955-8304 Petr V. Nazarov (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0003-3443-0298 Simone P. Niclou (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3417-9534 Alessandro Michelucci (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0003-1230-061X Anna Golebiewska (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-4160-2521
Point of Contact	Use email button above to contact. LIST QDKM (LIST)
Description	Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. Methods: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. Results: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood–brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. Conclusions: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment. Graphical Abstract: (Figure presented.) (2024-04-02) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1186/s13073-024-01321-8 for the original and latest version of the publication* (2026-07-01)
Subject	Medicine, Health and Life Sciences
Keyword	Microglia Tumor microenvironment Myeloid Glioma Phenotype Immune system Brain tumor Cancer research Transcriptome Biology Population Cell Immunology Medicine Pathology Inflammation Gene expression Gene Genetics
Topic Classification	Glioma Diagnosis and Treatment Immune cells in cancer Neuroinflammation and Neurodegeneration Mechanisms
Deposit Date	2024-04-02
Data Type	Article
Data Source	Genome Medicine

Dataset Terms

License/Data Use Agreement

Our Community Norms as well as good scientific practices expect that proper credit is given via citation. Please use the data citation shown on the dataset page.

Creative Commons Attribution 4.0 International License. CC BY 4.0

Dataset Version	Summary	Contributors	Published on
No records found.

Edit File

This file has already been deleted (or replaced) in the current version. It may not be edited.

Restrict Access

Restricting limits access to published files. People who want to use the restricted files can request access by default. If you disable request access, you must add information about access to the Terms of Access field.

Learn about restricting files and dataset access in the User Guide.

Request Access

Enable access request

You must enable request access or add terms of access to restrict file access.

Terms of Access for Restricted Files

Save Changes

Edit Embargo

The selected file or files have already been published. Contact an administrator to change the embargo date or reason of the file or files.

Edit Retention Period

The selected file or files have already been published. Contact an administrator to change the retention period date or reason of the file or files.

Delete Files

The file will be deleted after you click on the Delete button.

Files will not be removed from previously published versions of the dataset.

Select File(s)

Please select one or more files.

Share Dataset

Share this dataset on your favorite social media networks.

Continue

Dataset Citations

Citations for this dataset are retrieved from Crossref via DataCite using Make Data Count standards. For more information about dataset metrics, please refer to the User Guide.

Sorry, no citations were found.

Inaccessible Files Selected

The selected file(s) may not be downloaded because you have not been granted access or the file(s) have a retention period that has expired or the files can only be transferred via Globus.

You may request access to any restricted file(s) by clicking the Request Access button.

Ineligible Files Selected

The selected file(s) may not be transferred because you have not been granted access or the file(s) have a retention period that has expired or the files are not Globus accessible.

You may request access to any restricted file(s) by clicking the Request Access button.

Download Options

The files selected are too large to download as a ZIP.

You can select individual files that are below the 100.0 MB download limit from the files table, or use the Data Access API for programmatic access to the files.

Select File(s)

Please select a file or files to be downloaded.

Inaccessible Files Selected

The selected file(s) may not be downloaded because you have not been granted access or the file(s) have a retention period that has expired.

Click Continue to download the files you have access to download.

Ineligible Files Selected

Some file(s) cannot be transferred. (They are restricted, embargoed, with an expired retention period, or not Globus accessible.)

Click Continue to transfer the elligible files.

Delete Dataset

Are you sure you want to delete this dataset and all of its files? You cannot undelete this dataset.

Delete Draft Version

Are you sure you want to delete this draft version? Files will be reverted to the most recently published version. You cannot undelete this draft.

Unpublished Dataset Preview URL

Preview URL can only be used with unpublished versions of datasets.

Unpublished Dataset Preview URL

Are you sure you want to disable the Preview URL? If you have shared the Preview URL with others they will no longer be able to use it to access your unpublished dataset.

Delete Files

The file(s) will be deleted after you click on the Delete button.

Files will not be removed from previously published versions of the dataset.

Compute

This dataset contains restricted files you may not compute on because you have not been granted access.

Deaccession Dataset

Are you sure you want to deaccession? This is permanent and the selected version(s) will no longer be viewable by the public.

Deaccession Dataset

Are you sure you want to deaccession this dataset? This is permanent an it will no longer be viewable by the public.

Version Differences Details

Please select two versions to view the differences.

Version Differences Details

Version:
Last Updated:

Select File(s)

Please select a file or files for access request.

Select File(s)

Embargoed files cannot be accessed. Please select an unembargoed file or files for your access request.

Edit Tags

Select existing file tags or create new tags to describe your files. Each file can have more than one tag.

Request Access

You need to Log In to request access.

Dataset Terms

Please confirm and/or complete the information needed below in order to request access to files in this dataset.

This dataset is made available under the following terms. Please confirm and/or complete the information needed below in order to continue.

License/Data Use Agreement

Our Community Norms as well as good scientific practices expect that proper credit is given via citation. Please use the data citation shown on the dataset page.

Creative Commons Attribution 4.0 International License. CC BY 4.0

Preview Guestbook

Upon downloading files the guestbook asks for the following information.

Guestbook Name

Collected Data

Account Information

Package File Download

Use the Download URL in a Wget command or a download manager to download this package file. Download via web browser is not recommended. User Guide - Downloading a Dataverse Package via URL

Download URL

https://lore.list.lu/api/access/datafile/

Compute Batch

Clear Batch

Dataset	Persistent Identifier	Change Compute Batch

Compute Batch

Submit for Review

You will not be able to make changes to this dataset while it is in review.

Publish Dataset

Are you sure you want to republish this dataset?

Select if this is a minor or major version update.

Minor Release (1.1)

Major Release (2.0)

Publish Dataset

This dataset cannot be published until LIST Open Repository is published by its administrator.

Return to Author

Return this dataset to contributor for modification. The reason for return entered below will be sent by email to the author.

Curation Status History

Status	Date	Assigner
No records found.

Add/Edit a Version Note

Styled Citation