Comprehensive Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Transcriptional Signatures of Macrophages in Intrahepatic Cholestasis of Pregnancy

作者：Mi Tang, Liling Xiong, Jianghui Cai, Xuejia Gong, Fan Li, Xiaoyu Zhou, Shasha Xing, Xiao Yang · 发表于：Journal of Inflammation Research · 年份：2024 · DOI：10.2147/jir.s471374 · 被引用次数：5 · 研究领域：Drug Transport and Resistance Mechanisms、Pregnancy and Medication Impact、Single-cell and spatial transcriptomics

Purpose: Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated. Patients and Methods: Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta. Results: In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories sho...