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NuMorph:组织透明化全脑图像中皮质细胞表型分析的工具。

NuMorph: Tools for cortical cellular phenotyping in tissue-cleared whole-brain images.

机构信息

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27514, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

出版信息

Cell Rep. 2021 Oct 12;37(2):109802. doi: 10.1016/j.celrep.2021.109802.

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.

摘要

组织透明化方法允许在不进行物理切片的情况下对小鼠大脑中的每个细胞进行成像。然而,目前用于清除组织图像中细胞定量的计算工具仅限于对典型小鼠中稀疏细胞群进行计数。在这里,我们介绍了 NuMorph,这是一组分析工具,可在通过光片显微镜清除和成像后对小鼠皮层内的所有核和核标记物进行定量。我们应用 NuMorph 来研究两种不同的小鼠模型:一种拓扑异构酶 1(Top1)模型,具有严重的神经退行性缺陷,另一种神经纤维瘤素 1(Nf1)模型,具有更微妙的大脑过度生长表型。在每种情况下,我们都确定了基因缺失对单个细胞类型计数和在皮层区域分布的差异影响,这些影响表现为大脑形态的总体改变。这些结果强调了全脑成像方法的价值,并且这些工具广泛适用于以细胞分辨率研究大脑结构表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a1c/8530274/d61594dc2c44/nihms-1747911-f0002.jpg

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