RNA-Seq investigations of human post-mortem trigeminal ganglia.
RNA-Seq investigations of human post-mortem trigeminal ganglia.
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DOI：
10.1177/0333102417720216
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Mannes AJ
中科院分区：
文献类型：
--
作者：
LaPaglia DM;Sapio MR;Burbelo PD;Thierry-Mieg J;Thierry-Mieg D;Raithel SJ;Ramsden CE;Iadarola MJ;Mannes AJ
三叉神经节包含将痛觉、触觉、压感和许多其他躯体感觉方式传递到中枢神经系统的神经元。神经节也是潜伏的疱疹病毒1型感染的蓄水池。为了更好地了解导致偏头痛和头痛的分子因素，对尸检的人三叉神经节进行了转录组分析。在16个人三叉神经节的小亚区进行了基因表达的RNA-Seq测量。这些样本还鉴定了来自病毒和微生物基因组的转录本。用荧光素酶免疫沉淀法检测血液中的单纯疱疹病毒1型抗体。观察到的分子异质性可以通过取样切除神经节解剖上不同的亚区来解释，这些亚区与神经元富集区和非神经富集区一致，即雪旺细胞富集区。在三叉神经节中检测到的HSV-1转录本水平与血液中HSV-1抗体水平相关。多个偏头痛易感基因在神经丰富的三叉神经样本中强烈表达，而其他基因在血管中表达。这些数据提供了一个全面的人类三叉神经转录组，并通过广泛的质量控制和RNA-Seq方法的精细化下游分析，为评估不均匀的死后组织提供了一个框架。通过基因关联确定的偏头痛易感基因的表达谱似乎强调了三叉神经血管系统的血管成分。与背根节相比，其他基因在三叉神经节中的表达丰富，对家族性偏头痛潜在的KCNK18基因的深入转录分析表明，在两个特定的神经节神经元群体中有选择性的神经表达。这些数据表明，偏头痛相关基因的表达谱可以扩展和放大从遗传关联研究中获得的潜在神经生物学见解。
The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia. The samples were also characterized for transcripts derived from viral and microbial genomes. Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the luciferase immunoprecipitation assay. Observed molecular heterogeneity could be explained by sampling of anatomically distinct sub-regions of the excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann cell, enriched subregions. The levels of HSV-1 transcripts detected in trigeminal ganglia correlated with blood levels of HSV-1 antibodies. Multiple migraine susceptibility genes were strongly expressed in neurally-enriched trigeminal samples, while others were expressed in blood vessels. These data provide a comprehensive human trigeminal transcriptome and a framework for evaluation of inhomogeneous post-mortem tissues through extensive quality control and refined downstream analyses for RNA-Seq methodologies. Expression profiling of migraine susceptibility genes identified by genetic association appears to emphasize the blood vessel component of the trigeminovascular system. Other genes displayed enriched expression in the trigeminal compared to dorsal root ganglion, and in-depth transcriptomic analysis of the KCNK18 gene underlying familial migraine shows selective neural expression within two specific populations of ganglionic neurons. These data suggest that expression profiling of migraine-associated genes can extend and amplify the underlying neurobiological insights obtained from genetic association studies.
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影响因子：
6.1
作者：
IADAROLA, MJ;OFRI, D;KLEINMAN, JE
通讯作者：
KLEINMAN, JE
影响因子：
48
作者：
Dodick, David W.;Goadsby, Peter J.;Grayzel, David S.
通讯作者：
Grayzel, David S.
DOI：
10.1016/j.jpain.2014.09.010
发表时间：
2014-12
期刊：
The journal of pain
影响因子：
--
作者：
Goswami SC;Mishra SK;Maric D;Kaszas K;Gonnella GL;Clokie SJ;Kominsky HD;Gross JR;Keller JM;Mannes AJ;Hoon MA;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
3.3
作者：
Goswami SC;Thierry-Mieg D;Thierry-Mieg J;Mishra S;Hoon MA;Mannes AJ;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
48
作者：
Engstrom, Par G.;Steijger, Tamara;Sipos, Botond;Grant, Gregory R.;Kahles, Andre;Raetsch, Gunnar;Goldman, Nick;Hubbard, Tim J.;Harrow, Jennifer;Guigo, Roderic;Bertone, Paul
通讯作者：
Bertone, Paul