Reis Clovis F, de Souza Iara D, Morais Diego A A, Oliveira Raffael A C, Imparato Danilo O, de Almeida Rita M C, Dalmolin Rodrigo J S
Bioinformatics Multidisciplinary Environment - IMD, Federal University of Rio Grande do Norte, Natal, Brazil.
Institute of Physics and National Institute of Science and Technology: Complex Systems, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Front Genet. 2019 Sep 10;10:791. doi: 10.3389/fgene.2019.00791. eCollection 2019.
Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells' ability to differentiate, therefore influencing ES-NP cells' fate.
铅中毒的影响广泛，包括神经系统损伤，尤其是在发育过程中，会导致神经损伤。铅与含钙和锌的金属蛋白相互作用会广泛影响细胞代谢，因为这些蛋白质与细胞内离子平衡、信号转导级联反应的激活以及基因表达调控有关。尽管铅被认为是一种神经毒素，但在铅对神经细胞中整个细胞系统转录的全局影响方面，仍存在知识空白。为了从系统的角度研究铅中毒的影响，我们在经30 µM醋酸铅处理26天的人胚胎来源神经祖细胞（ES-NP细胞）的RNA测序数据集中应用了转录图谱方法。我们观察到与细胞分化相关的几个细胞系统早期下调，如细胞骨架组织、RNA和蛋白质生物合成。下调的细胞系统呈现出大且紧密相连的网络。对于长时间处理（12至26天），可以观察到细胞转录谱有大量损伤。综合富集的术语来看，我们观察到从染色质重塑到囊泡运输的基因表达调控的所有层面都受到干扰。鉴于ES-NP细胞是能够产生其他神经细胞类型的祖细胞，我们的结果表明铅诱导的基因表达紊乱可能会损害细胞的分化能力，从而影响ES-NP细胞的命运。
