基于条件细胞特异性网络的 2 型糖尿病潜在网络标志物和信号通路研究。
Research on Potential Network Markers and Signaling Pathways in Type 2 Diabetes Based on Conditional Cell-Specific Network.
机构信息
School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang 471023, China.
出版信息
Genes (Basel). 2022 Jun 26;13(7):1155. doi: 10.3390/genes13071155.
Traditional methods concerning type 2 diabetes (T2D) are limited to grouped cells instead of each single cell, and thus the heterogeneity of single cells is erased. Therefore, it is still challenging to study T2D based on a single-cell and network perspective. In this study, we construct a conditional cell-specific network (CCSN) for each single cell for the GSE86469 dataset which is a single-cell transcriptional set from nondiabetic (ND) and T2D human islet samples, and obtain a conditional network degree matrix (CNDM). Since beta cells are the key cells leading to T2D, we search for hub genes in CCSN of beta cells and find that is essential for regulation and storage of insulin, and the renin-angiotensin system involving is related to most pathological processes leading to diabetic nephropathy. The communication between beta cells and other endocrine cells is performed and three gene pairs with obvious interaction are found. In addition, different expression genes (DEGs) are found based on CNDM and the gene expression matrix (GEM), respectively. Finally, 'dark' genes are identified, and enrichment analysis shows that is involved in the VEGF signaling pathway and indirectly affects the production of Prostacyclin (PGI), which may be a potential biomarker for diabetic nephropathy.
传统的 2 型糖尿病(T2D)方法仅限于分组细胞,而不是每个单独的细胞,因此单个细胞的异质性被抹去。因此,基于单细胞和网络的视角来研究 T2D 仍然具有挑战性。在这项研究中,我们为 GSE86469 数据集的每个单细胞构建了一个条件细胞特异性网络(CCSN),该数据集是来自非糖尿病(ND)和 T2D 人胰岛样本的单细胞转录组,获得了条件网络度矩阵(CNDM)。由于β细胞是导致 T2D 的关键细胞,我们在β细胞的 CCSN 中寻找枢纽基因,发现 对于胰岛素的调节和储存至关重要,涉及 的肾素-血管紧张素系统与导致糖尿病肾病的大多数病理过程有关。β细胞与其他内分泌细胞之间的通讯是通过网络实现的,发现了三个具有明显相互作用的基因对。此外,基于 CNDM 和基因表达矩阵(GEM)分别找到了差异表达基因(DEGs)。最后,确定了“暗”基因,富集分析表明 参与了 VEGF 信号通路,并间接影响了前列环素(PGI)的产生,这可能是糖尿病肾病的潜在生物标志物。