TRAP-seq defines markers for novel populations of hypothalamic and brainstem LepRb neurons.
TRAP-seq defines markers for novel populations of hypothalamic and brainstem LepRb neurons.
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陷阱seq定义了下丘脑和脑干LEPB神经元的新型标记。
DOI：
10.1016/j.molmet.2015.01.012
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发表时间：
2015-04
影响因子：
8.1
通讯作者：
Olson DP
中科院分区：
文献类型：
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作者：
Allison MB;Patterson CM;Krashes MJ;Lowell BB;Myers MG Jr;Olson DP
瘦素通过其受体（LepRb）作用于大脑中的多个LepRb神经元亚群，每个亚群控制能量平衡的特定方面。尽管含有LepRb的神经元的重要性，许多LepRb亚群的转录组和分子身份仍然不确定，由于难以研究异质脑区中LepRb神经元所代表的总细胞的一小部分。在这里，我们试图直接检查LepRb神经元的转录组，并确定功能相关的LepRb亚群的标记物。我们通过翻译核糖体亲和纯化（TRAP）从小鼠下丘脑和脑干LepRb细胞中分离mRNA，并通过RNA-seq（TRAP-seq）对其进行分析。来自LepRb细胞的TRAP mRNA富集肽能神经元的标记物，而来自非LepRb细胞的TRAP耗尽的mRNA富集神经胶质细胞和免疫细胞的标记物。下丘脑和脑干TRAP mRNA中富集的分泌蛋白编码基因揭示了LepRb神经元的亚群，其中含有以前未用作LepRb神经元功能标记的神经肽编码基因（包括强啡肽原，Pdyn）。此外，Pdyncre介导的Pdyn表达神经元（LepRbPdynKO小鼠）中Leprflox的消融减弱了能量消耗，从而在高脂肪喂养期间促进肥胖。CNS LepRb神经元的TRAP-seq定义了LepRb神经元转录组，并揭示了先前未识别的LepRb神经元亚群的新标记物。
Leptin acts via its receptor (LepRb) on multiple subpopulations of LepRb neurons in the brain, each of which controls specific aspects of energy balance. Despite the importance of LepRb-containing neurons, the transcriptome and molecular identity of many LepRb subpopulations remain undefined due to the difficulty of studying the small fraction of total cells represented by LepRb neurons in heterogeneous brain regions. Here we sought to examine the transcriptome of LepRb neurons directly and identify markers for functionally relevant LepRb subsets. We isolated mRNA from mouse hypothalamic and brainstem LepRb cells by Translating Ribosome Affinity Purification (TRAP) and analyzed it by RNA-seq (TRAP-seq). TRAP mRNA from LepRb cells was enriched for markers of peptidergic neurons, while TRAP-depleted mRNA from non-LepRb cells was enriched for markers of glial and immune cells. Genes encoding secreted proteins that were enriched in hypothalamic and brainstem TRAP mRNA revealed subpopulations of LepRb neurons that contained neuropeptide-encoding genes (including prodynorphin, Pdyn) not previously used as functional markers for LepRb neurons. Furthermore, Pdyncre-mediated ablation of Leprflox in Pdyn-expressing neurons (LepRbPdynKO mice) blunted energy expenditure to promote obesity during high-fat feeding. TRAP-seq of CNS LepRb neurons defines the LepRb neuron transcriptome and reveals novel markers for previously unrecognized subpopulations of LepRb neurons.
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影响因子：
16.2
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
通讯作者：
Lowelll, BB
影响因子：
29
作者：
Dodd GT;Worth AA;Nunn N;Korpal AK;Bechtold DA;Allison MB;Myers MG Jr;Statnick MA;Luckman SM
通讯作者：
Luckman SM
DOI：
10.1152/ajpendo.00643.2012
发表时间：
2013-05-01
影响因子：
5.1
作者：
Laque, Amanda;Zhang, Yan;Muenzberg, Heike
通讯作者：
Muenzberg, Heike
影响因子：
15.9
作者：
Berglund, Eric D.;Vianna, Claudia R.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.
刺激性室室核向AGRP神经元电路，驱动饥饿。
影响因子：
64.8
作者：
通讯作者：
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