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Whole Human-Brain Mapping of Single Cortical Neurons for Profiling Morphological Diversity and Stereotypy
bioRxiv - Neuroscience Pub Date : 2022-10-30 , DOI: 10.1101/2022.10.29.514375
Xiaofeng Han , Shuxia Guo , Nan Ji , Tian Li , Jian Liu , Xiangqiao Ye , Yi Wang , Zhixi Yun , Feng Xiong , Jing Rong , Di Liu , Hui Ma , Yujin Wang , Yue Huang , Peng Zhang , Wenhao Wu , Liya Ding , Michael Hawrylycz , Ed Lein , Giorgio A. Ascoli , Wei Xie , Lijuan Liu , Liwei Zhang , Hanchuan Peng

Quantification of individual cells' morphology and their distribution at the whole brain scale is essential to understand the structure and diversity of cell types. Despite recent technological advances, especially single cell labeling and whole brain imaging, for many prevailing animal models, it is exceedingly challenging to reuse similar technologies to study human brains. Here we propose Adaptive Cell Tomography (ACTomography), a low-cost, high-throughput, high-efficacy tomography approach, based on adaptive targeting of individual cells suitable for human-brain scale modeling of single neurons to characterize their 3-D structures, statistical distributions, and extensible for other cellular features. Specifically, we established a platform to inject dyes into cortical neurons in surgical tissues of 18 patients with brain tumors or other conditions and 1 donated fresh postmortem brain. We collected 3-D images of 1746 cortical neurons, of which 852 neurons were subsequentially reconstructed to quantify their local dendritic morphology, and mapped to standard atlases both computationally and semantically. In our data, human neurons are more diverse across brain regions than by subject age or gender. The strong stereotypy within cohorts of brain regions allows generating a statistical tensor-field of neuron morphology to characterize 3-D anatomical modularity of a human brain.

中文翻译:

用于分析形态多样性和刻板印象的单个皮质神经元的全人脑映射

对单个细胞的形态及其在全脑范围内的分布进行量化对于了解细胞类型的结构和多样性至关重要。尽管最近的技术进步,特别是单细胞标记和全脑成像,对于许多流行的动物模型来说,重复使用类似的技术来研究人类大脑是极具挑战性的。在这里,我们提出了自适应细胞断层扫描 (ACTomography),这是一种低成本、高通量、高效的断层扫描方法,基于对单个细胞的自适应靶向,适用于单个神经元的人脑尺度建模以表征其 3-D 结构,统计分布,并且可扩展为其他细胞特征。具体来说,我们建立了一个平台,将染料注射到 18 名脑肿瘤或其他疾病患者的手术组织中的皮质神经元中,其中 1 名捐赠了新鲜的死后大脑。我们收集了 1746 个皮层神经元的 3-D 图像,其中 852 个神经元随后被重建以量化其局部树突形态,并在计算和语义上映射到标准图谱。在我们的数据中,与受试者年龄或性别相比,人类神经元在大脑区域的差异更大。大脑区域群内的强烈刻板印象允许生成神经元形态的统计张量场来表征人脑的 3-D 解剖模块性。其中 852 个神经元随后被重建以量化其局部树突形态,并在计算和语义上映射到标准图谱。在我们的数据中,与受试者年龄或性别相比,人类神经元在大脑区域的差异更大。大脑区域群内的强烈刻板印象允许生成神经元形态的统计张量场来表征人脑的 3-D 解剖模块性。其中 852 个神经元随后被重建以量化其局部树突形态,并在计算和语义上映射到标准图谱。在我们的数据中,与受试者年龄或性别相比,人类神经元在大脑区域的差异更大。大脑区域群内的强烈刻板印象允许生成神经元形态的统计张量场来表征人脑的 3-D 解剖模块性。
更新日期:2022-10-31
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