Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing.
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing.
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DOI：
10.1016/j.molmet.2017.02.007
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发表时间：
2017-05
影响因子：
8.1
通讯作者：
Yeo GSH
中科院分区：
文献类型：
--
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
弓状前阿黑皮素（POMC）神经元是控制体重的关键节点。通常简单地描述为瘦素的直接靶点，最近的数据表明了一个更复杂的结构。使用单细胞RNA测序，我们已经产生了在小鼠POMC神经元的基因表达图谱。在163个神经元中，118个表达高水平的Pomc，几乎没有/没有Agrp表达，被认为是“典型的”POMC神经元（P+）。其他45/163表达低水平的Pomc和高水平的Agrp（A+P+）。P+神经元的无偏聚类分析揭示了四个不同的类，每个类具有不同的细胞表面受体基因表达谱。此外，只有12%（14/118）的P+神经元表达瘦素受体（Lepr），而58%（26/45）的A+P+神经元。相比之下，胰岛素受体（Insr）在P+和A+P+神经元上以相似的频率表达（分别为64%和55%）。这些数据表明弓形POMC神经元是一个高度异质性的人口。登录号：GSE 92707。下丘脑POMC神经元是异质性的，大致可分为4组。细胞表面受体是分离的主要驱动因素。出乎意料的是，28%的POMC细胞显示出典型的AgRP/NPY神经元的特征。只有12%表达瘦素受体，表明瘦素的反应可能是间接的。
Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. Of 163 neurons, 118 expressed high levels of Pomc with little/no Agrp expression and were considered “canonical” POMC neurons (P+). The other 45/163 expressed low levels of Pomc and high levels of Agrp (A+P+). Unbiased clustering analysis of P+ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P+ neurons expressed the leptin receptor (Lepr) compared with 58% (26/45) of A+P+ neurons. In contrast, the insulin receptor (Insr) was expressed at similar frequency on P+ and A+P+ neurons (64% and 55%, respectively). These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707. Hypothalamic POMC neurons are heterogeneous and can broadly divided into 4 groups. Cell surface receptors are major drivers for the segregation. Unexpectedly, 28% of POMC-cells show signatures typical of AgRP/NPY neurons. Only 12% express leptin receptor, indicating response to leptin is likely indirect.