A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.
A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.
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DOI：
10.1016/j.molmet.2021.101240
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发表时间：
2021-11
影响因子：
8.1
通讯作者：
Yeo GSH
中科院分区：
文献类型：
--
作者：
Dowsett GKC;Lam BYH;Tadross JA;Cimino I;Rimmington D;Coll AP;Polex-Wolf J;Knudsen LB;Pyke C;Yeo GSH
位于后脑的最后区（AP）和孤束核（NTS）是感受和整合外周营养信号从而调节摄食行为的关键核团。虽然单细胞转录组学已被用于小鼠，以揭示基因表达谱和异质性的关键下丘脑人口，类似的深入研究尚未在后脑进行。使用单核RNA测序，我们提供了在进食和禁食状态下小鼠AP和NTS内的16，034个细胞的详细调查。其中，8，910个是神经元，分为30个簇，其中4，289个来自自由进食的小鼠，4，621个来自过夜禁食的小鼠。共有7，124个细胞核来自非神经元细胞，包括少突胶质细胞、星形胶质细胞和小胶质细胞。有趣的是，我们发现少突胶质细胞群体对过夜禁食特别敏感。分别结合GLP 1、GIP、GDF 15和胰淀素的受体GLP 1R、GIPR、GFRAL和CALCR都在后脑中表达，并且是抗肥胖治疗的主要靶标。我们对这四个群体的转录组进行了分析，结果表明，他们的基因表达谱并没有因为一夜禁食而发生显著改变。值得注意的是，我们发现大约一半表达GIPR的细胞是少突胶质细胞。此外，我们对后脑内表达POMC的神经元进行了分析，并证明84%的POMC神经元表达PCSK 1、PSCK 2或两者，这意味着黑皮质素肽可能是由这些神经元产生的。我们提供了一个详细的单细胞水平表征的AP和NTS细胞表达受体的关键抗肥胖药物，无论是已经批准用于人类使用或在临床试验。这一资源将有助于阐明这些化合物有效性的机制，并证明在继续寻找其他新的治疗靶点方面是有用的。我们通过单核RNA测序提供了在进食和禁食状态下的小鼠AP和NTS的16，034个细胞的调查。8，910个被分为30个神经元簇，7，124个是非神经元的，如少突胶质细胞、星形胶质细胞和小胶质细胞。我们研究了表达Glp1r、Gipr、Gfral、Calcr和Pomc的人群的转录组。过夜禁食不会显著改变上述群体的表达谱。我们提供了一个详细的单细胞水平表征的AP和NTS细胞表达抗肥胖药物的目标。
The area postrema (AP) and nucleus tractus solitarius (NTS) located in the hindbrain are key nuclei that sense and integrate peripheral nutritional signals and consequently regulate feeding behaviour. While single-cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain. Using single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of mice in the fed and fasted states. Of these, 8,910 were neurons that group into 30 clusters, with 4,289 from mice fed ad libitum and 4,621 from overnight fasted mice. A total of 7,124 nuclei were from non-neuronal cells, including oligodendrocytes, astrocytes, and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL, and CALCR, which bind GLP1, GIP, GDF15, and amylin, respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC-expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2, or both, implying that melanocortin peptides are likely produced by these neurons. We provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds and also prove useful in the continued search for other novel therapeutic targets. We provide a survey of 16,034 cells of the murine AP and NTS in the fed and fasted state by single-nucleus RNA sequencing. 8,910 are grouped into 30 neuronal clusters, and 7,124 are non-neuronal such as oligodendrocytes, astrocytes and microglia. We examine the transcriptomes of populations expressing Glp1r, Gipr, Gfral, Calcr, and Pomc. The expression profiles for the above populations were not dramatically altered by an overnight fast. We provide a detailed single-cell level characterisation of AP and NTS cells expressing anti-obesity drug targets.
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影响因子：
14.8
作者：
Krishnaswami SR;Grindberg RV;Novotny M;Venepally P;Lacar B;Bhutani K;Linker SB;Pham S;Erwin JA;Miller JA;Hodge R;McCarthy JK;Kelder M;McCorrison J;Aevermann BD;Fuertes FD;Scheuermann RH;Lee J;Lein ES;Schork N;McConnell MJ;Gage FH;Lasken RS
通讯作者：
Lasken RS
影响因子：
82.9
作者：
Emmerson, Paul J.;Wang, Feng;Wu, Xinle
通讯作者：
Wu, Xinle
影响因子：
8.1
作者：
Lam BYH;Cimino I;Polex-Wolf J;Nicole Kohnke S;Rimmington D;Iyemere V;Heeley N;Cossetti C;Schulte R;Saraiva LR;Logan DW;Blouet C;O'Rahilly S;Coll AP;Yeo GSH
通讯作者：
Yeo GSH
影响因子：
14.9
作者：
McCarthy DJ;Chen Y;Smyth GK
通讯作者：
Smyth GK
影响因子：
3.7
作者：
Bakken, Trygve E.;Hodge, Rebecca D.;Tasic, Bosiljka
通讯作者：
Tasic, Bosiljka