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灵长类动物脉络丛发育过程中转录组变化及功能注释

Transcriptomal changes and functional annotation of the developing non-human primate choroid plexus.

机构信息

Department of Physiology, Institute for Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy Gothenburg, Sweden.

Department of Obstetrics, Center for Pregnancy and Newborn Research, The University of Texas Health Science Center San Antonio, TX, USA.

出版信息

Front Neurosci. 2015 Mar 12;9:82. doi: 10.3389/fnins.2015.00082. eCollection 2015.

Abstract

The choroid plexuses are small organs that protrude into each brain ventricle producing cerebrospinal fluid that constantly bathes the brain. These organs differentiate early in development just after neural closure at a stage when the brain is little vascularized. In recent years the plexus has been shown to have a much more active role in brain development than previously appreciated thereby it can influence both neurogenesis and neural migration by secreting factors into the CSF. However, much of choroid plexus developmental function is still unclear. Most previous studies on this organ have been undertaken in rodents but translation into humans is not straightforward since they have a different timing of brain maturation processes. We have collected choroid plexus from three fetal gestational ages of a non-human primate, the baboon, which has much closer brain development to humans. The transcriptome of the plexuses was determined by next generation sequencing and Ingenuity Pathway Analysis software was used to annotate functions and enrichment of pathways of changes in the transcriptome. The number of unique transcripts decreased with development and the majority of differentially expressed transcripts were down-regulated through development suggesting a more complex and active plexus earlier in fetal development. The functional annotation indicated changes across widespread biological functions in plexus development. In particular we find age-dependent regulation of genes associated with annotation categories: Gene Expression, Development of Cardiovascular System, Nervous System Development and Molecular Transport. Our observations support the idea that the choroid plexus has roles in shaping brain development.

摘要

脉络丛是突出到每个脑室内的小器官,产生不断浸润大脑的脑脊液。这些器官在神经闭合后不久的发育早期就开始分化,此时大脑的血管化程度还很低。近年来,脉络丛在大脑发育中的作用比以前认识到的更为活跃,通过将因子分泌到脑脊液中,它可以影响神经发生和神经迁移。然而,脉络丛的许多发育功能仍不清楚。大多数关于该器官的先前研究都是在啮齿动物中进行的,但向人类的转化并不简单,因为它们的大脑成熟过程的时间不同。我们从非人类灵长类动物狒狒的三个胎儿胎龄收集了脉络丛,其大脑发育与人类更为接近。通过下一代测序确定了脉络丛的转录组,并用 Ingenuity Pathway Analysis 软件注释了转录组变化的功能和途径富集。独特转录本的数量随着发育而减少,大多数差异表达的转录本随着发育而下调,这表明在胎儿发育早期,脉络丛更加复杂和活跃。功能注释表明,在脉络丛发育过程中,广泛的生物学功能发生了变化。特别是,我们发现与基因表达、心血管系统发育、神经系统发育和分子转运等注释类别的基因随年龄呈依赖性调节。我们的观察结果支持脉络丛在塑造大脑发育中起作用的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77dc/4357249/c680353933c8/fnins-09-00082-g0001.jpg

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