Preparation, construction and high-throughput automated analysis of human brain tissue microarrays for neurodegenerative disease drug development

Malvindar K. Singh-Bains, Nasim F. Mehrabi, Adelie Y. S. Tan, Richard L. M. Faull, Mike Dragunow

Published: 2021-03-18 DOI: 10.1038/s41596-021-00503-7

Drug Discovery

Neurodegenerative Diseases

High-Throughput Analysis

Tissue Microarrays

Automated Platforms

AI 解读

Supplementary information

Supplementary Table 1

Supplementary Table 1 contains example data outputs generated from count nuclei (gray heading), neurite outgrowth (pink heading) and optical density scaled (yellow heading) Metamorph journals

Author Correction: Full-length sequencing of circular DNA viruses and extrachromosomal circular DNA using CIDER-Seq

Generation of heart-forming organoids from human pluripotent stem cells

Design and fabrication of wearable electronic textiles using twisted fiber-based threads

Activation of mechanoluminescent nanotransducers by focused ultrasound enables light delivery to deep-seated tissue in vivo

Chromatin accessibility profiling by ATAC-seq

Deoxyfluorination of phenols for chemoselective18F-labeling of peptides

Author Correction: cfSNV: a software tool for the sensitive detection of somatic mutations from cell-free DNA

Human primordial germ cell-like cells specified from resetting precursors develop in human hindgut organoids

An inexpensive semi-automated sample processing pipeline for cell-free RNA extraction

Application of CHyMErA Cas9-Cas12a combinatorial genome-editing platform for genetic interaction mapping and gene fragment deletion screening

查看全部

Sections

Figures

References

Supplementary information

Dragunow, M. Human brain neuropharmacology: a platform for translational neuroscience. Trends Pharmacol. Sci. 41, 777–792 (2020).
Singh-Bains, M. K. et al. Altered microglia and neurovasculature in the Alzheimer’s disease cerebellum. Neurobiol. Dis. 132, 104589 (2019).
Coppieters, N. et al. Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain. Neurobiol. Aging 35, 1334–1344 (2014).
Narayan, P. J. et al. Assessing fibrinogen extravasation into Alzheimer’s disease brain using high-content screening of brain tissue microarrays. J. Neurosci. Methods 247, 41–49 (2015).
Narayan, P. J., Lill, C., Faull, R., Curtis, M. A. & Dragunow, M. Increased acetyl and total histone levels in post-mortem Alzheimer’s disease brain. Neurobiol. Dis. 74, 281–294 (2015).
Dominy, S. S. et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 5, eaau3333 (2019).
Singh‐Bains, M. K. et al. Globus pallidus degeneration and clinico‐pathological features of Huntington’s disease. Ann. Neurol. 80, 185–201 (2016).
Singh‐Bains, M. K. et al. Cerebellar degeneration correlates with motor symptoms in Huntington disease. Ann. Neurol. 85, 396–405 (2019).
Mehrabi, N. F. et al. Symptom heterogeneity in Huntington’s disease correlates with neuronal degeneration in the cerebral cortex. Neurobiol. Dis. 96, 67–74 (2016).
Kim, E. H. et al. Cortical interneuron loss and symptom heterogeneity in Huntington disease. Ann. Neurol. 75, 717–727 (2014).
Thu, D. C. et al. Cell loss in the motor and cingulate cortex correlates with symptomatology in Huntington’s disease. Brain 133, 1094–1110 (2010).
Nana, A. L. et al. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington’s disease. J. Huntingtons Dis. 3, 45–64 (2014).
West, M. J. Design-based stereological methods for counting neurons. Prog. Brain Res. 135, 43–51 (2002).
Kononen, J. et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4, 844–847 (1998).
Alkushi, A. et al. Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Arch. 442, 271–277 (2003).
Garcıa, J. F. et al. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 101, 681–689 (2003).
Makretsov, N. A. et al. Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast carcinoma. Clin. Cancer Res. 10, 6143–6151 (2004).
Giltnane, J. M. & Rimm, D. L. Technology insight: identification of biomarkers with tissue microarray technology. Nat. Clin. Pract. Oncol. 1, 104–111 (2004).
Camp, R. L., Dolled-Filhart, M., King, B. L. & Rimm, D. L. Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res. 63, 1445–1448 (2003).
Martikainen, P., Louhelainen, A.-M., Kauppinen, T. & Alafuzoff, I. Human brain tissue microarrays as a platform to investigate diseases of the nervous system. Brain Res. 1089, 33–43 (2006).
Dancau, A.-M., Simon, R., Mirlacher, M. & Sauter, G. in Cancer Gene Profiling 53–65 (Springer, 2016).
Yang, P., Waldvogel, H., Turner, C., Faull, R. & Dragunow, M. Vascular remodelling is impaired in Parkinson disease. J. Alzheimers Dis. Parkinsonism 7, 2161–0460.1000313 (2017).
Hewitt, S. M. in Molecular Profiling 201–214 (Springer, 2012).
Eguiluz, C., Viguera, E., Millán, L. & Pérez, J. Multitissue array review: a chronological description of tissue array techniques, applications and procedures. Pathol. Res. Pract. 202, 561–568 (2006).
Tzankov, A., Went, P., Zimpfer, A. & Dirnhofer, S. Tissue microarray technology: principles, pitfalls and perspectives—lessons learned from hematological malignancies. Exp. Gerontol. 40, 737–744 (2005).
Hassan, S., Ferrario, C., Mamo, A. & Basik, M. Tissue microarrays: emerging standard for biomarker validation. Curr. Opin. Biotechnol. 19, 19–25 (2008).
Packeisen, J., Korsching, E., Herbst, H., Boecker, W. & Buerger, H. Demystified…tissue microarray technology. Mol. Pathol. 56, 198 (2003).
Simon, R. in Tissue Microarrays 1–16 (Springer, 2010).
Hutchins, G. & Grabsch, H. I. How to make tissue microarrays. Diagn. Histopathol. 24, 127–135 (2018).
Nedjadi, T. et al. Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques. BMC Cancer 16, 653 (2016).
Plum, P. S. et al. HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma. BMC Cancer 19, 38 (2019).
Parsons, M. & Grabsch, H. How to make tissue microarrays. Diagn. Histopathol. 15, 142–150 (2009).
Gulmann, C. & O’Grady, A. Tissue microarrays: an overview. Curr. Diagn. Pathol. 9, 149–154 (2003).
Dragunow, M. The adult human brain in preclinical drug development. Nat. Rev. Drug Discov. 7, 659–666 (2008).
Kauppinen, T., Martikainen, P. & Alafuzoff, I. Human postmortem brain tissue and 2-mm tissue microarrays. Appl. Immunohistochem. Mol. Morphol. 14, 353–359 (2006).
Sjöbeck, M., Haglund, M., Persson, A., Sturesson, K. & Englund, E. Brain tissue microarrays in dementia research: white matter microvascular pathology in Alzheimer’s disease. Neuropathology 23, 290–295 (2003).
Wang, H., Wang, H., Zhang, W. & Fuller, G. N. Tissue microarrays: applications in neuropathology research, diagnosis, and education. Brain Pathol. 12, 95–107 (2002).
Goldstine, J., Seligson, D. B., Beizai, P., Miyata, H. & Vinters, H. V. Tissue microarrays in the study of non-neoplastic disease of the nervous system. J. Neuropathol. Exp. Neurol. 61, 653–662 (2002).
Walker, L. et al. Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts. J. Neural Transm. 124, 671–683 (2017).
Eckel-Passow, J. E. et al. Tissue microarrays: one size does not fit all. Diagn. Pathol. 5, 48 (2010).
Dhir, R. in Tissue Proteomics (eds Liu, B. C. S. & Ehrlich, J. R.) 91–103 (Humana Press, 2008).
Gately, K., Kerr, K. & O’Byrne, K. in Gene Expression Profiling 139–153 (Springer, 2011).
Hegde, R. N. et al. TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington’s disease models. EMBO J. 39, e104671 (2020).
Waldvogel, H. et al. The collection and processing of human brain tissue for research. Cell Tissue Bank. 9, 169–179 (2008).
Waldvogel, H. J., Curtis, M. A., Baer, K., Rees, M. I. & Faull, R. L. M. Immunohistochemical staining of post-mortem adult human brain sections. Nat. Protoc. 1, 2719–2732 (2006).
Howat, W. J. & Wilson, S. J. in Tissue Microarrays 63–72 (Springer, 2010).
Mirra, S. S. et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41, 479–479 (1991).
Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 (1991).
Wan, W.-H., Fortuna, M. B. & Furmanski, P. A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J. Immunol. Methods 103, 121–129 (1987).
Vogel, U. F. The construction of high-density paraffin tissue microarrays with 0.43-mm-diameter paraffin tissue core biopsies is technically feasible. Virchows Arch. 453, 43–46 (2008).
Narayan, P. et al. Inconsistencies in histone acetylation patterns among different HD model systems and HD post-mortem brains. Neurobiol. Dis. 146, 105092 (2020).
Bolton, K. L. et al. Assessment of automated image analysis of breast cancer tissue microarrays for epidemiologic studies. Cancer Epidemiol. Biomark. Prev. 19, 992–999 (2010).
Braun, M. et al. Quantification of protein expression in cells and cellular subcompartments on immunohistochemical sections using a computer supported image analysis system. Histol. Histopathol. 28, 605–610 (2013).
Camp, R. L., Chung, G. G. & Rimm, D. L. Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat. Med. 8, 1323–1328 (2002).
Dolled-Filhart, M. et al. in Tissue Microarrays 151–162 (Springer, 2010).
Ryan, D., Mulrane, L., Rexhepaj, E. & Gallagher, W. M. in Drug Safety Evaluation 97–112 (Springer, 2011).
Loughrey, M. B. et al. Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis. Histopathology 73, 327–338 (2018).
Dragunow, M. High-content analysis in neuroscience. Nat. Rev. Neurosci. 9, 779–788 (2008).
Wang, F. et al. RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J. Mol. Diagn. 14, 22–29 (2012).

Preparation, construction and high-throughput automated analysis of human brain tissue microarrays for neurodegenerative disease drug development

Supplementary information

推荐阅读