Astrocyte molecular signatures in Huntington’s disease
Open accessAbstract
Astrocyte gene expression is altered in mouse models of Huntington’s disease and in postmortem brain samples from patients with HD.
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Only a subset, often a mix of A1 and A2 or pan-reactive transcripts, are upregulated in astrocytes from brains of study participants with HD or AD, or from several mouse models of acute injuries and chronic diseases of the CNS.
“Importantly, only a subset, often a mix of A1 and A2 or pan-reactive transcripts, are upregulated in astrocytes from brains of study participants with HD74 or AD75,76, or from several mouse models of acute injuries and chronic diseases of the CNS42,69,76,77.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [69]
Reactive astrocytes are diverse, as demonstrated by transcriptomic profiling of mouse bulk astrocytes or preselected astrocyte populations.
“Likewise, reactive astrocytes are also diverse, as unequivocally demonstrated by microarray-based66–68 and RNAseq-based48,69–71 transcriptomic profiling of mouse bulk astrocytes48,66–70 or of astrocyte populations preselected according to cell-surface markers71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [69]
Transcriptomic profiling shows that reactive astrocytes adopt distinct molecular states in different disease models, in different CNS regions, and in brain tumors.
“Such transcriptomic profiling specifically shows that reactive astrocytes adopt distinct molecular states in different disease models48,66–70, in different CNS regions70, and in brain tumors71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [69]
Cites
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Glia — more than just brain glue
Allen, N. J., & Barres, B. A. (2009) · Nature · doi:10.1038/457675a · Cited by 856 · see citing works
Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice
Langfelder, P., Cantle, J. P., Chatzopoulou, D., Wang, N., Gao, F., Al-Ramahi, I., Lu, X.-H., Ramos, E. M., El-Zein, K., Zhao, Y., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4256 · Cited by 385 · see citing works
Self-citationDo glia drive synaptic and cognitive impairment in disease?
Chung, W.-S., Welsh, C. A., Barres, B. A., & Stevens, B. (2015) · Nature Neuroscience · doi:10.1038/nn.4142 · Cited by 385 · see citing works
Matos, M., Shen, H.-Y., Augusto, E., Wang, Y., Wei, C. J., Wang, Y. T., Agostinho, P., Boison, D., Cunha, R. A., & Chen, J.-F. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.026 · Cited by 153 · see citing works
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Reactive astrocyte nomenclature, definitions, and future directions
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,533 · see citing works
Self-citationFunction and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders
Brandebura, A. N., Paumier, A., Onur, T. S., & Allen, N. J. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-022-00641-1 · Cited by 427 · see citing works
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Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?
Liddelow, S. A., Marsh, S. E., & Stevens, B. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.006 · Cited by 226 · see citing works
Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury
Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107776 · Cited by 221 · see citing works
Neuroinflammation in Huntington’s Disease: A Starring Role for Astrocyte and Microglia
Saba, J., Couselo, F. L., Bruno, J., Carniglia, L., Durand, D., Lasaga, M., & Caruso, C. (2022) · Current Neuropharmacology · doi:10.2174/1570159x19666211201094608 · Cited by 117 · see citing works
The contribution of glial cells to Huntington's disease pathogenesis
Wilton, D. K., & Stevens, B. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104963 · Cited by 112 · see citing works
Glia in neurodegeneration: Drivers of disease or along for the ride?
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What are activated and reactive glia and what is their role in neurodegeneration?
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Calì, C., Cantando, I., Veloz Castillo, M. F., Gonzalez, L., & Bezzi, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168922 · Cited by 66 · see citing works
Freel, B. A., Kelvington, B. A., Sengupta, S., Mukherjee, M., & Francis, K. R. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049843 · Cited by 17 · see citing works
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“…looked at the transcriptional profile of astrocytes in disease models and have shown transcriptional differences between astrocytes associated with Huntington’s disease (Al-Dalahmah et al., 2020; Diaz-Castro et al., 2019), AD (Habib et al., 2020; Xu et al., 2020), or aging (Pan et al., 2020).”
Background
- Authors
- Diaz-Castro, B., Gangwani, M. R., Yu, X., Coppola, G., & Khakh, B. S.
- Affiliations
- Department of Physiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
- University of California, Los Angeles (US)
- Corresponding author
- Khakh, Baljit S.
- Venue
- Science Translational Medicine
- Published
- 2019-10-16
- Volume
- 11
- Issue
- 514
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2981248429
- Cited by
- 255
- References
- 6
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 40 · 2023: 44 · 2022: 63 · 2021: 39 · 2020: 25
- FWCI
- 15.29
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Institute of Neurological Disorders and Stroke (NS111583)
- National Institute of Child Health and Human Development (U54HD087101)
- American Heart Association (16POST27260256)
- CHDI Foundation (A-12226)
- NIMH (MH099559, MH104069)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Huntington's disease, astrocytes, striatum, gene expression signatures, mutant huntingtin, neurodegeneration, mouse model, disease stage
- MeSH terms
- Huntingtin Protein, Animals, Astrocytes, Disease Models, Animal, Humans, Huntington Disease, Neurons, Systems Biology, Mice
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