Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan.
Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan.
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DOI：
10.3390/ijms221910387
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发表时间：
2021-09-27
影响因子：
5.6
通讯作者：
Alachkar A
中科院分区：
文献类型：
--
作者：
Chen S;Alhassen W;Vakil Monfared R;Vachirakorntong B;Nauli SM;Baldi P;Alachkar A
几乎所有脑细胞表面都有初级纤毛，这是一种类似触角的微管感觉细胞器，在脑功能中发挥着关键作用。在神经发育阶段，纤毛对于大脑的形成和成熟至关重要。在成人大脑中，纤毛作为信号枢纽发挥着重要作用，能够接收和转导各种信号，并调节细胞间通讯。这些不同的作用表明，纤毛的功能，甚至结构，在人类一生中会发生变化。为了进一步了解纤毛功能随年龄的变化，我们识别并分析了人类一生中纤毛结构和功能组件表达的年龄依赖性模式。我们从BrainSpan图谱获取了16个脑区的纤毛转录组数据，并使用线性回归模型通过计算回归系数来分析年龄依赖性表达模式。我们发现，67%的纤毛转录本是至少在一个脑区随年龄差异表达的基因（DEGAs）。年龄依赖性表达具有区域特异性，腹外侧前额叶皮质中DEGAs的数量最多，而海马体中最少。在大多数脑区，大多数纤毛DEGAs随年龄上调。编码纤毛基体组件的转录本构成了纤毛DEGAs的大部分，相邻的大脑皮质表现出大量重叠的纤毛DEGAs对。最值得注意的是，特定的α/β - 微管蛋白亚基（TUBA1A、TUBB2A和TUBB2B）和SNAP - 25在几乎所有脑区中，分别呈现出随年龄下降和上升的最高速率。已知α/β - 微管蛋白和SNAP - 25的表达在与年龄相关的神经发育和神经退行性疾病中会失调。我们的研究结果支持了纤毛结构和功能组件在一生中的高度动态变化在脑回路正常生理过程中的作用。此外，这些结果表明纤毛信号在与年龄相关的精神/神经疾病的病理生理机制中起着关键作用。
Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia’s structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/β-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/β-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.
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初级纤毛和树突棘：不同但相似的信号传导室。
影响因子：
3.8
作者：
Nechipurenko, Inna V.;Doroquez, David B.;Sengupta, Piali
通讯作者：
Sengupta, Piali
影响因子：
4.2
作者：
Baldi, Pierre;Alhassen, Wedad;Alachkar, Amal
通讯作者：
Alachkar, Amal
影响因子：
8.8
作者：
Boonsawat, Paranchai;Joset, Pascal;Rauch, Anita
通讯作者：
Rauch, Anita
DOI：
10.1093/database/bap022
发表时间：
2009
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Arnaiz O;Malinowska A;Klotz C;Sperling L;Dadlez M;Koll F;Cohen J
通讯作者：
Cohen J
DOI：
10.1073/pnas.0804558105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Breunig, Joshua J.;Sarkisian, Matthew R.;Town, Terrence
通讯作者：
Town, Terrence