Cultured <i>ex vivo</i> human brain tissue maintains cell-type transcriptional identities

Abstract There is growing recognition of the need for human-based models of the nervous system and its diseases. Studies have investigated the electrophysiological properties of neurons in ex vivo human brain tissue, but the maintenance of other cell types remains unclear. We therefore used single-nucleus RNA sequencing of six patient samples to determine how well various cell types maintain their transcriptional identities over two weeks in organotypic slice culture (day 0, with 83,501 nuclei, and day 14, with 45,738). For each patient sample (two pediatric temporal lobectomies, one adult frontal cortex, two glioblastomas, and one medulloblastoma), we generated correlations between each day 0 and day 14 cell type using the extent of up- or down-regulation of all significantly variable genes. We found generally high correlations, especially in tumor cells (glioblastoma tumor cells r = 0.89, medulloblastoma tumor cells r = 0.93), with microglia (r = 0.86), oligodendrocytes (r = 0.80), pericytes (r = 0.77), endothelial cells (r = 0.78), and fibroblasts (r = 0.76). This holds significant promise for this model’s use in both mechanistic studies and therapeutic screens, with its high degree of molecular and cellular relevance to the in vivo human brain.

Authors

Institutions

Publication Details

Journal
Brain Communications
Published
2026-03-07
DOI
https://doi.org/10.1093/braincomms/fcag073
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Cultured ex vivo human brain tissue maintains cell-type transcriptional identities

Guillermo Aldave, A. Jalali, Evelyne K. Tantry, Snigdha Srivastava et al.
Brain Communications
Glioma Diagnosis and Treatment
article

Cultured ex vivo human brain tissue maintains cell-type transcriptional identities

Guillermo Aldave, A. Jalali, Evelyne K. Tantry, Snigdha Srivastava, Melissa M. Blessing, Daniel J. Curry, Benjamin Russell Arenkiel, Kalman A. Katlowitz, Naser Jaleel, Suyang Bao, Nisha Gadgil, Emily Ji, Howard L. Weiner, Samuel G. McClugage, David F. Bauer, G.V. Rao, Angela P. Addison, Akash J. Patel, Shankar P. Gopinath, Maria Guevara, Akdes Serin Harmanci, Sai Mallannagari, Maria Morkas, William E Whitehead, Omar Tanweer, Carrie A Mohila, Benjamin D W Belfort, Joshua Ortiz-Guzman, J P McGinnis, Sameer A Sheth
article en

Abstract

Abstract There is growing recognition of the need for human-based models of the nervous system and its diseases. Studies have investigated the electrophysiological properties of neurons in ex vivo human brain tissue, but the maintenance of other cell types remains unclear. We therefore used single-nucleus RNA sequencing of six patient samples to determine how well various cell types maintain their transcriptional identities over two weeks in organotypic slice culture (day 0, with 83,501 nuclei, and day 14, with 45,738). For each patient sample (two pediatric temporal lobectomies, one adult frontal cortex, two glioblastomas, and one medulloblastoma), we generated correlations between each day 0 and day 14 cell type using the extent of up- or down-regulation of all significantly variable genes. We found generally high correlations, especially in tumor cells (glioblastoma tumor cells r = 0.89, medulloblastoma tumor cells r = 0.93), with microglia (r = 0.86), oligodendrocytes (r = 0.80), pericytes (r = 0.77), endothelial cells (r = 0.78), and fibroblasts (r = 0.76). This holds significant promise for this model’s use in both mechanistic studies and therapeutic screens, with its high degree of molecular and cellular relevance to the in vivo human brain.

Brain Communications
Texas Medical Center (US), Baylor College of Medicine (US), Neurological Research Institute (US), Texas Children's Hospital (US), Baylor Genetics (US)
Openalex Percentile: Top 29%
Glioma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.