Multi-omics and spatial analysis of microgravity-grown glioblastoma organoids reveal superior modeling of advanced disease after long-term spaceflight
- 1Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556
- 2Space Tango, Limited Liability Company, Lexington, KY 40505
- 3Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801
Abstract
Creating accurate organoid models remains a challenge, particularly for diseases like glioblastoma (GBM), an aggressive, treatment-resistant brain cancer with an immunosuppressive microenvironment. To overcome limitations of Earth-based models (sedimentation and disaggregation) and leverage the unique advantages of space (accelerated disease progression and immune dysregulation), this study utilizes a panel of GBM-myeloid organoids cultured for 40 d aboard the International Space Station. Spaceflight-grown GBM organoids have more uniform morphology compared to ground controls. We observed a context-dependent response to spaceflight, with the inclusion of macrophages and monocytes altering the bulk and spatial transcriptional response. While GBM-alone organoids have transcriptional markers of less aggressive disease in microgravity, organoids containing GBM cells + monocytes have increased expression of genes associated with disease progression and poor patient outcomes. Gene expression patterns are more spatially organized, with mesenchymal-related genes enriched in the core and inflammation-related genes enriched at the periphery, mimicking GBM tumor architecture. Microgravity-grown GBM+monocyte organoids exhibit increased secretion of proteins such as CXCL12 and LOX-1, associated with more aggressive disease. Infrared chemical imaging confirms spatial chemical gradients of DNA, protein, and lipid species in both space- and terrestrially-grown organoids. In summary, this work presents not only an advanced model of glioblastoma for basic and translational research but also demonstrates methods to acquire diverse data from organoids compatible with the unique constraints of in-space systems, helping establish a working model for orbital oncology.
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BibTeX
@article{darantiere2026multiomics,
title = {{Multi-omics and spatial analysis of microgravity-grown glioblastoma organoids reveal superior modeling of advanced disease after long-term spaceflight}},
author = {Alice Burchett Darantiere and Maksym Zarodniuk and Shelby Giza and Jason Rexroat and Paul Kuehl and Twyman Clements and Keerthiveena Balraj and Haley Marco and Alura D’Souza and Julian Najera and Rohit Bhargava and Meenal Datta},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2616218123},
url = {https://doi.org/10.1073/pnas.2616218123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Multi-omics and spatial analysis of microgravity-grown glioblastoma organoids reveal superior modeling of advanced disease after long-term spaceflight
AU - Alice Burchett Darantiere
AU - Maksym Zarodniuk
AU - Shelby Giza
AU - Jason Rexroat
AU - Paul Kuehl
AU - Twyman Clements
AU - Keerthiveena Balraj
AU - Haley Marco
AU - Alura D’Souza
AU - Julian Najera
AU - Rohit Bhargava
AU - Meenal Datta
PY - 2026
DA - 2026/10/21
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2616218123
UR - https://doi.org/10.1073/pnas.2616218123
AB - Creating accurate organoid models remains a challenge, particularly for diseases like glioblastoma (GBM), an aggressive, treatment-resistant brain cancer with an immunosuppressive microenvironment. To overcome limitations of Earth-based models (sedimentation and disaggregation) and leverage the unique advantages of space (accelerated disease progression and immune dysregulation), this study utilizes a panel of GBM-myeloid organoids cultured for 40 d aboard the International Space Station. Spaceflight-grown GBM organoids have more uniform morphology compared to ground controls. We observed a context-dependent response to spaceflight, with the inclusion of macrophages and monocytes altering the bulk and spatial transcriptional response. While GBM-alone organoids have transcriptional markers of less aggressive disease in microgravity, organoids containing GBM cells + monocytes have increased expression of genes associated with disease progression and poor patient outcomes. Gene expression patterns are more spatially organized, with mesenchymal-related genes enriched in the core and inflammation-related genes enriched at the periphery, mimicking GBM tumor architecture. Microgravity-grown GBM+monocyte organoids exhibit increased secretion of proteins such as CXCL12 and LOX-1, associated with more aggressive disease. Infrared chemical imaging confirms spatial chemical gradients of DNA, protein, and lipid species in both space- and terrestrially-grown organoids. In summary, this work presents not only an advanced model of glioblastoma for basic and translational research but also demonstrates methods to acquire diverse data from organoids compatible with the unique constraints of in-space systems, helping establish a working model for orbital oncology.
SN - 0027-8424
SN - 1091-6490
ER -