Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Clin Lab, BGI Genomics, Shijiazhuang, China.
BGI Genomics, Shenzhen, China.
Life Sci Alliance. 2024 Jun 26;7(9). doi: 10.26508/lsa.202302394. Print 2024 Sep.
Genome-wide association studies have identified over 200 genetic loci associated with inflammatory bowel disease; however, the mechanism of such a large amount of susceptibility genes remains uncertain. In this study, we integrated bioinformatics analysis and two independent single-cell transcriptome datasets to investigate the expression network of 232 susceptibility genes in Crohn's disease (CD) patients and healthy controls. The study revealed that most of the susceptibility genes are specifically and strictly expressed in the monocytes of the human intestinal tract. The susceptibility genes established a network within the monocytes of health control. The robustness of a gene network may prevent disease onset that is influenced by the genetic and environmental alteration in the expression of susceptibility genes. In contrast, we showed a sparse network in pediatric/adult CD patients, suggesting the broken network contributed to the CD etiology. The network status of susceptibility genes at the single-cell level of monocytes provided novel insight into the etiology.
全基因组关联研究已经确定了 200 多个与炎症性肠病相关的遗传位点；然而，如此大量的易感基因的机制仍不确定。在这项研究中，我们整合了生物信息学分析和两个独立的单细胞转录组数据集，以研究克罗恩病（CD）患者和健康对照者中 232 个易感基因的表达网络。研究表明，大多数易感基因在人类肠道的单核细胞中特异性和严格表达。易感基因在健康对照组的单核细胞内建立了一个网络。基因网络的稳健性可能会阻止疾病的发生，因为易感基因的表达受到遗传和环境改变的影响。相比之下，我们在儿科/成年 CD 患者中显示出稀疏的网络，这表明该网络的破坏可能导致 CD 的发病机制。单核细胞单细胞水平上易感基因的网络状态为发病机制提供了新的见解。
