Brain atlas for glycoprotein hormone receptors at single-transcript level.
Brain atlas for glycoprotein hormone receptors at single-transcript level.
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DOI：
10.7554/elife.79612
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发表时间：
2022-09-02
期刊：
影响因子：
7.7
通讯作者：
Zaidi, Mone
中科院分区：
文献类型：
--
作者：
Ryu, Vitaly;Gumerova, Anisa;Korkmaz, Funda;Kang, Seong Su;Katsel, Pavel;Miyashita, Sari;Kannangara, Hasni;Cullen, Liam;Chan, Pokman;Kuo, TanChun;Padilla, Ashley;Sultana, Farhath;Wizman, Soleil A.;Kramskiy, Natan;Zaidi, Samir;Kim, Se-Min;New, Maria, I;Rosen, Clifford J.;Goosens, Ki A.;Frolinger, Tal;Haroutunian, Vahram;Ye, Keqiang;Lizneva, Daria;Davies, Terry F.;Yuen, Tony;Zaidi, Mone
关键词：
越来越多的证据表明，垂体前叶激素，传统上认为有单一的功能，在调节单一的内分泌靶点，作用于多个身体组织，如骨，脂肪和肝脏。也有新的证据表明，垂体前叶激素作用于脑受体，介导中枢神经和外周躯体功能。在这里，我们创建了最全面的TSHR，LHCGR和FSHR表达的神经解剖图谱。我们已经使用RNAscope，一种允许在单转录水平检测mRNA的技术，连同蛋白质水平验证，以记录Tshr表达在173和Fshr表达在353个脑区，核和亚核中使用立体定位坐标中的小鼠脑图谱鉴定。我们还确定了401个脑区，核和亚核Lhcgr转录。作为补充，我们使用ViewRNA，另一种单转录本检测技术，来建立人脑样本中FSHR的表达，其中转录本共定位于MALAT1阳性神经元中。此外，我们发现这三种受体在心室区域都有高表达，但功能尚不清楚。有趣的是，Tshr和Fshr在第三脑室室管膜层的表达分别类似于甲状腺滤泡细胞和睾丸支持细胞。相比之下，Fshr定位于小鼠和人脑齿状回颗粒层的NeuN阳性神经元，两者都是阿尔茨海默病的易感区域。因此，我们的图谱为科学家探索大脑糖蛋白激素受体的刺激或失活与体细胞功能之间的联系提供了重要的资源。通过进一步的研究，可能会发现人类疾病的新的可行途径。
There is increasing evidence that anterior pituitary hormones, traditionally thought to have unitary functions in regulating single endocrine targets, act on multiple somatic tissues, such as bone, fat, and liver. There is also emerging evidence for anterior pituitary hormone action on brain receptors in mediating central neural and peripheral somatic functions. Here, we have created the most comprehensive neuroanatomical atlas on the expression of TSHR, LHCGR, and FSHR. We have used RNAscope, a technology that allows the detection of mRNA at single-transcript level, together with protein level validation, to document Tshr expression in 173 and Fshr expression in 353 brain regions, nuclei and subnuclei identified using the Atlas for the Mouse Brain in Stereotaxic Coordinates. We also identified Lhcgr transcripts in 401 brain regions, nuclei and subnuclei. Complementarily, we used ViewRNA, another single-transcript detection technology, to establish the expression of FSHR in human brain samples, where transcripts were co-localized in MALAT1-positive neurons. In addition, we show high expression for all three receptors in the ventricular region—with yet unknown functions. Intriguingly, Tshr and Fshr expression in the ependymal layer of the third ventricle was similar to that of the thyroid follicular cells and testicular Sertoli cells, respectively. In contrast, Fshr was localized to NeuN-positive neurons in the granular layer of the dentate gyrus in murine and human brain—both are Alzheimer’s disease-vulnerable regions. Our atlas thus provides a vital resource for scientists to explore the link between the stimulation or inactivation of brain glycoprotein hormone receptors on somatic function. New actionable pathways for human disease may be unmasked through further studies.