NuMorph: Tools for cortical cellular phenotyping in tissue-cleared whole-brain images
| Autor: | Jason L. Stein, Lei Xing, Tianyi Liu, Mark J. Zylka, Benjamin W. Rees, Guorong Wu, Oleh Krupa, Giulia Fragola, Jessica T. Mory, Ellie Hadden-Ford, Ashok Krishnamurthy, William D. Snider, Zachary Humphrey |
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| Rok vydání: | 2021 |
| Předmět: |
Support Vector Machine
Cell Neuroimaging Biology Article General Biochemistry Genetics and Molecular Biology Genes Neurofibromatosis 1 Image Processing Computer-Assisted medicine Animals Cell Nucleus Cerebral Cortex Mice Knockout Neurons Histocytological Preparation Techniques Mouse cortex Brain morphometry Phenotype Neurofibromin 1 medicine.anatomical_structure DNA Topoisomerases Type I Cellular resolution Nerve Degeneration biology.protein Analysis tools Neuroglia Neuroscience Gene Deletion Clearance |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Tissue-clearing methods allow every cell in the mouse brain to be imaged without physical sectioning. However, the computational tools currently available for cell quantification in cleared tissue images have been limited to counting sparse cell populations in stereotypical mice. Here, we introduce NuMorph, a group of analysis tools to quantify all nuclei and nuclear markers within the mouse cortex after clearing and imaging by light-sheet microscopy. We apply NuMorph to investigate two distinct mouse models: a Topoisomerase 1 (Top1) model with severe neurodegenerative deficits and a Neurofibromin 1 (Nf1) model with a more subtle brain overgrowth phenotype. In each case, we identify differential effects of gene deletion on individual cell-type counts and distribution across cortical regions that manifest as alterations of gross brain morphology. These results underline the value of whole-brain imaging approaches, and the tools are widely applicable for studying brain structure phenotypes at cellular resolution. Graphical abstract In brief Krupa et al. develop an image analysis toolbox called NuMorph that accurately quantifies all nuclei within the mouse cortex after tissue clearing and light-sheet imaging. They implement NuMorph to characterize region- and cell-type-specific deficits present in two distinct mouse models, demonstrating the advantages of a whole-brain imaging approach. |
| Databáze: | OpenAIRE |
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