单细胞测序揭示下丘脑细胞对社会行为的控制

　　美国加州理工学院David J. Anderson小组取得一项新进展，他们利用单细胞测序对控制社会行为下丘脑节点的细胞类型进行了多模式分析。相关论文发表在2019年10月17日出版的《细胞》杂志上。

　　研究人员介绍，腹内侧下丘脑的腹侧分支（VMHvl）包含约4000个神经元，这些神经元投射到多个目标并控制与生俱来的社会行为，包括侵略和坐骑。然而，VMHv1中的细胞类型的数目及其与连通性和行为功能的关系是未知的。

　　研究人员使用了两个独立的平台：SMART-seq（约4500个神经元）和10x（约78000个神经元）进行了单细胞RNA测序，并分别研究了转录组学特征与轴突预测或行为激活之间的对应关系。典型相关分析（CCA）确定了17个转录组类型（T类型），包括几个性双态群体，其中大多数已通过seqFISH验证。

　　早期基因分析确定了对入侵者雄性和雌性表现出优先反应的T类型，但仅是行为特异性激活的罕见例子。出乎意料的是，许多VMHvl T类型包含具有不同投影目标偏好的混合神经元群体。总体而言，这些分析表明，令人惊讶的是，很少有VMHvl T类型表现出与特定于行为的激活和连通性明确的对应关系。

　　附：英文原文

　　Title: Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

　　Author: Dong-Wook Kim, Zizhen Yao, Lucas T. Graybuck, Tae Kyung Kim, Thuc Nghi Nguyen, Kimberly A. Smith, Olivia Fong, Lynn Yi, Noushin Koulena, Nico Pierson, Sheel Shah, Liching Lo, Allan-Hermann Pool, Yuki Oka, Lior Pachter, Long Cai, Bosiljka Tasic, Hongkui Zeng, David J. Anderson

　　Issue&Volume: 2019/10/17

　　Abstract:

　　The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) contains ∼4,000 neurons that project to multiple targets and control innate social behaviors including aggression and mounting. However, the number of cell types in VMHvl and their relationship to connectivity and behavioral function are unknown. We performed single-cell RNA sequencing using two independent platforms—SMART-seq (∼4,500 neurons) and 10x (∼78,000 neurons)—and investigated correspondence between transcriptomic identity and axonal projections or behavioral activation, respectively. Canonical correlation analysis (CCA) identified 17 transcriptomic types (T-types), including several sexually dimorphic clusters, the majority of which were validated by seqFISH. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity.

　　DOI: 10.1016/j.cell.2019.09.020

　　Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31071-2

　　期刊信息

　　Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216

　　官方网址：https://www.cell.com/

　　投稿链接：https://www.editorialmanager.com/cell/default.aspx