Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain
Open accessAbstract
Human diseases are often accompanied by histological changes that confound interpretation of molecular analyses and identification of disease-related effects. We developed population-specific expression analysis (PSEA), a computational method of analyzing gene expression in samples of varying composition that can improve analyses of quantitative molecular data in many biological contexts. PSEA of brains from individuals with Huntington's disease revealed myelin-related abnormalities that were undetected using standard differential expression analysis.
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The primary cultures used for expression analyses represented the intended cell populations, as confirmed by immunocytochemistry and largely segregated expression of cell-type-specific mRNAs.
“The cellular composition of these cultures was verified by immunocytochemistry using antibodies against well established cell-type-specific marker antigens: NeuN/Rbfox (neuronal nuclear antigen/RNA binding protein Fox) for mature neurons, GFAP (glial fibrillary acidic protein) for astrocytes, O4 antigen for oligodendrocytes, and integrin ␣ M chain (Itgam) for microglia (Kuhn et al., 2011).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Kuhn et al., 2011
Brain parenchyma is principally composed of the four neural cell types (neurons, astrocytes, oligodendrocytes, and microglia), with insignificant contributions from endothelial cells, pericytes, fibroblasts, smooth muscle cells, and erythrocytes.
“As we have shown in recent cell-resolved analyses of brain tissue, brain parenchyma is principally composed of the 4 neural cell types (neurons, astrocytes, oligodendrocytes, and microglia), with insignificant contributions from endothelial cells, pericytes, fibroblasts, smooth muscle cells, and erythrocytes (Kuhn et al., 2011).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Kuhn et al., 2011
Purifying cell populations or performing single-cell transcriptional analyses can identify important changes not apparent in whole-tissue transcriptomes.
“Purifying cell populations or carrying out transcriptional analyses on single cells158–163 can identify important changes that are not apparent in whole-tissue transcriptomes141,142.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [142]
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- Authors
- Kuhn, A., Thu, D., Waldvogel, H. J., Faull, R. L. M., & Luthi-Carter, R.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- University of Auckland (NZ)
- Corresponding author
- Kuhn, Alexandre
- Venue
- Nature Methods
- Published
- 2011-10-09
- Volume
- 8
- Issue
- 11
- Pages
- 945-947
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2093358653
- Cited by
- 195
- References
- 23
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 17 · 2022: 10 · 2021: 21 · 2020: 18 · 2019: 12 · 2018: 24 · 2017: 14 · 2016: 17 · 2015: 12 · 2014: 13 · 2013: 14 · 2012: 7
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- gene expression analysis, Huntington's disease, brain tissue composition, myelin abnormalities, differential gene expression
- MeSH terms
- Brain Diseases, Humans, Gene Expression Profiling
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