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

Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior.
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DOI:
10.1016/j.cell.2019.09.020
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发表时间:
2019-10-17
期刊:
影响因子:
64.5
通讯作者:
Anderson DJ
Anderson DJ
中科院分区:
生物学1区
文献类型:
--
作者:
Kim DW;Yao Z;Graybuck LT;Kim TK;Nguyen TN;Smith KA;Fong O;Yi L;Koulena N;Pierson N;Shah S;Lo L;Pool AH;Oka Y;Pachter L;Cai L;Tasic B;Zeng H;Anderson DJ

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下丘脑腹内侧的腹外侧亚区(VMHvl)包含约4,000个神经元,它们投射到多个目标并控制包括攻击和骑乘在内的先天社会行为。然而,VMHvl中细胞类型的数量及其与连接和行为功能的关系是未知的。我们使用两个独立的平台-SMART-seq(~ 4,500个神经元)和10 x(~ 78,000个神经元)-进行了单细胞RNA测序,并分别研究了转录组身份与轴突投射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型),包括几个性二态性集群,其中大部分是由seqFISH验证。立即早期基因分析确定的T型表现出优先响应入侵男性与女性,但只有罕见的例子,行为特异性激活。出乎意料的是,许多VMHvl T型包括具有不同投射目标偏好的神经元的混合群体。总体而言,我们的分析显示,令人惊讶的是,很少有VMHvl T型表现出与行为特异性激活和连接的明确对应。对小鼠腹内侧下丘脑腹外侧亚区的单细胞RNA测序,揭示了雄性和雌性之间存在差异的几种转录组细胞类型。下丘脑腹内侧是一个包含约4,000个神经元并控制先天社会行为(包括攻击和安装)的大脑区域。
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. Single-cell RNA sequencing of the mouse ventrolateral subdivision of the ventromedial hypothalamus, a brain region that contains ~4,000 neurons and controls innate social behaviors including aggression and mounting, reveals several transcriptomic cell types that differ between males and females.
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