1. NuMorph: Tools for cortical cellular phenotyping in tissue-cleared whole-brain images.
- Author
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Krupa O, Fragola G, Hadden-Ford E, Mory JT, Liu T, Humphrey Z, Rees BW, Krishnamurthy A, Snider WD, Zylka MJ, Wu G, Xing L, and Stein JL
- Subjects
- Animals, Cell Nucleus metabolism, Cerebral Cortex metabolism, DNA Topoisomerases, Type I deficiency, DNA Topoisomerases, Type I genetics, Gene Deletion, Genes, Neurofibromatosis 1, Image Processing, Computer-Assisted, Mice, Knockout, Neuroglia metabolism, Neurons metabolism, Phenotype, Support Vector Machine, Mice, Cell Nucleus pathology, Cerebral Cortex pathology, Histocytological Preparation Techniques, Nerve Degeneration, Neuroglia pathology, Neuroimaging, Neurons pathology
- Abstract
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., Competing Interests: Declaration of interests O.K. is currently employed at Scribe Therapeutics., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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