小柯机器人

美国加州大学圣迭戈分校Edward M. Callaway等研究人员合作揭示神经元表观组学与远距离投射的全脑对应关系。2023年12月13日，《自然》杂志在线发表了这项成果。

研究人员使用epi-retro-seq2，将单细胞表观基因组和细胞类型与整个小鼠大脑中33034个神经元的远距离投射联系起来，这些神经元来自32个不同区域，投射到24个不同目标（225个起源-到-目标组合）。研究人员重点介绍了这些数据的用途，这些数据可用于研究投射类型与转录组学和表观基因组学相关的原理，以及用于解决与遗传学相关的细胞类型和连接的假设。研究人员提供了一份总体综合报告，其中包含对投射到每个目标的神经元的可辨别性进行的926次统计比较。

研究人员将该数据集整合到由数百万个神经元组成的更大的BRAIN Initiative Cell Census Network图谱中，以便将投射细胞类型与一致集群联系起来。与空间转录组学的整合进一步将投射丰富的集群分配到比原始解剖更小的起源区域。研究人员通过对下丘脑、丘脑、后脑、杏仁核和中脑的投射神经元进行分析，深入了解了这些细胞类型的特性，包括差异表达基因、相关顺式调节元件和转录因子结合基序以及神经递质的使用。

据介绍，单细胞分析将大脑中数十亿个神经元解析为数千个“细胞类型”集群，这些集群居住在不同的大脑结构中。许多细胞类型通过有针对性的远距离投射来介导其功能，从而实现特定细胞类型之间的相互作用。

附：英文原文

Title: Brain-wide correspondence of neuronal epigenomics and distant projections

Author: Zhou, Jingtian, Zhang, Zhuzhu, Wu, May, Liu, Hanqing, Pang, Yan, Bartlett, Anna, Peng, Zihao, Ding, Wubin, Rivkin, Angeline, Lagos, Will N., Williams, Elora, Lee, Cheng-Ta, Miyazaki, Paula Assakura, Aldridge, Andrew, Zeng, Qiurui, Salinda, J. L. Angelo, Claffey, Naomi, Liem, Michelle, Fitzpatrick, Conor, Boggeman, Lara, Yao, Zizhen, Smith, Kimberly A., Tasic, Bosiljka, Altshul, Jordan, Kenworthy, Mia A., Valadon, Cynthia, Nery, Joseph R., Castanon, Rosa G., Patne, Neelakshi S., Vu, Minh, Rashid, Mohammad, Jacobs, Matthew, Ito, Tony, Osteen, Julia, Emerson, Nora, Lee, Jasper, Cho, Silvia, Rink, Jon, Huang, Hsiang-Hsuan, Pinto-Duartec, Antnio, Dominguez, Bertha, Smith, Jared B., OConnor, Carolyn, Zeng, Hongkui, Chen, Shengbo, Lee, Kuo-Fen, Mukamel, Eran A., Jin, Xin, Margarita Behrens, M., Ecker, Joseph R., Callaway, Edward M.

Issue&Volume: 2023-12-13

Abstract: Single-cell analyses parse the brain’s billions of neurons into thousands of ‘cell-type’ clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

DOI: 10.1038/s41586-023-06823-w

Source: https://www.nature.com/articles/s41586-023-06823-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html