A molecular census of arcuate hypothalamus and median eminence cell types.
A molecular census of arcuate hypothalamus and median eminence cell types.
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DOI：
10.1038/nn.4495
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发表时间：
2017-03
影响因子：
25
通讯作者：
Tsai LT
中科院分区：
文献类型：
--
作者：
Campbell JN;Macosko EZ;Fenselau H;Pers TH;Lyubetskaya A;Tenen D;Goldman M;Verstegen AM;Resch JM;McCarroll SA;Rosen ED;Lowell BB;Tsai LT
下丘脑丘脑腹侧正中隆起复合体（Arc-ME）通过分子上不同的细胞类型控制能量平衡、生育和生长，其中许多细胞类型仍然未知。为了以无偏见的方式对细胞类型进行分类，我们使用Drop-seq分析了成年小鼠Arc-ME中及其周围的20，921个单个细胞的基因表达。我们确定了50个转录不同的Arc-ME细胞群，包括一个罕见的伸展细胞群在Arc-ME扩散屏障，一个新的瘦素敏感神经元的人口，多种AgRP和POMC亚型，和食欲生长抑素神经元人口。我们扩展了Drop-seq来检测相关生理扰动的动态表达变化，揭示了细胞类型对能量状态的特异性反应，包括AgRP和POMC神经元的明显反应亚型。最后，将我们的数据与人类GWAS数据相结合，揭示了肥胖的遗传控制中两种以前未知的神经元亚型。该资源将通过提供对分子和细胞类型多样性的见解来加速生物发现，从中可以推断功能。
The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility, and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a novel leptin-sensing neuronal population, multiple AgRP and POMC subtypes, and an orexigenic somatostatin neuronal population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinctly responsive subtypes of AgRP and POMC neurons. Finally, integrating our data with human GWAS data implicates two previously unknown neuronal subtypes in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred.