PU.1 restores microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids.
Overview
- Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht 3584 CG, The Netherlands
- Princess Máxima Center for Pedriatic Onocology, Utrecht University, Utrecht 3584 CS, The Netherlands
- Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands
- Amsterdam Neuroscience, Cellular and Molecular Mechanisms, Amsterdam 1081 HV, The Netherlands
Abstract
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of upper and lower motor neurons and progressive muscle wasting. Accumulating evidence indicates a role for non-neuronal cells in ALS pathogenesis, but their exact role and mechanism-of-action remain incompletely understood. A hexanucleotide (GGGGCC) repeat expansion (HRE) in C9ORF72 is the most common genetic cause of ALS (C9-ALS) and a frequent cause of frontotemporal dementia (FTD).
Several lines of experimental evidence support a role for the immune system and microglia in C9-ALS/
Here, we show reduced cellular complexity and transcriptional changes in C9 neural organoid-derived microglia (C9-oMGs), involving phagocytic, lysosomal and immune response pathways. The release of inflammatory cues from C9-ALS/
Overall, our data demonstrate reduced microglial functions in a complex cellular disease environment and identify PU.1 as a potential target for restoring microglia changes in C9-ALS/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE284339, at NCBI GEO; found in “Data availability”
Data availability
All data supporting the findings of this study are available within the article and its Supplementary information. The RNA-seq data discussed in this publication have been deposited in the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus and are accessible through GEO Series accession number GSE284339: (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 11 MeSH terms, 6 funders, 88 references.
Cite
This paper
Ljubikj, T., Mars, M. Z., van der Geest, A. T., Jakobs, C. E., Bessler, N., Donega, V., van den Oetelaar, X. P. R. M., de Wit, M., & Pasterkamp, R. J. (2026). PU.1 restores microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids. Brain : a journal of neurology, 149(3), 801-817. https://
BibTeX
@article{ljubikj2026pu,
author = {Ljubikj, Tijana and Mars, Mayte Z and van der Geest, Astrid T and Jakobs, Channa E and Bessler, Nils and Donega, Vanessa and van den Oetelaar, Xynthia P R M and de Wit, Marina and Pasterkamp, R Jeroen},
title = {{PU.1 restores microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids}},
journal = {Brain : a journal of neurology},
year = {2026},
month = mar,
volume = {149},
number = {3},
pages = {801--817},
publisher = {Oxford University Press},
issn = {0006-8950},
doi = {10.1093/
url = {https://
pmid = {40966720},
pmcid = {PMC13016731}
}
RIS
TY - JOUR
AU - Ljubikj, Tijana
AU - Mars, Mayte Z
AU - van der Geest, Astrid T
AU - Jakobs, Channa E
AU - Bessler, Nils
AU - Donega, Vanessa
AU - van den Oetelaar, Xynthia P R M
AU - de Wit, Marina
AU - Pasterkamp, R Jeroen
TI - PU.1 restores microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids
T2 - Brain : a journal of neurology
J2 - Brain
PY - 2026
DA - 2026/
VL - 149
IS - 3
SP - 801
EP - 817
SN - 0006-8950
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
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"container-title": "Brain : a journal of neurology",
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