Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Characterization of chromatin accessibility in psoriasis / 医学前沿

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.

Using ATAC-seq to identify the chromatin accessibility activated by type I interferon in human monocytes / 上海交通大学学报（医学版）

Objective • To detect the genome-wide profiling of chromatin accessibility in human monocytes after stimulated with interferon α (IFNα). Methods • Blood samples were collected from a healthy donor. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) technique was performed to detect the chromatin accessibility. Bioinformatic tools were used for enrichment analysis and visual analysis. Results • With the treatment of IFNα, there were 430 significant up-regulated regions, and 442 significant down-regulated regions. Most of the accessible regions were located at promoters and the adjacent areas of the genes, followed by the intergenic areas and introns. The enrichment analysis showed that the genes related with up-regulated regions were enriched to interferon relevant pathways or anti-virus reactions. To visualize the corresponding chromatin regions, it showed that the intensity of ATAC-seq signal was significantly enhanced at the promoters and transcriptional start sites of effect or interferon-stimulated genes (ISGs) after IFNα stimulation; while for the regulatory ISGs, there was a certain degree of accessibility before stimulation, and the signal intensity was mildly improved. The motif analysis showed significant enrichment of interferon-stimulated response element and interferon regulatory factor in up-regulated regions. Conclusion • Chromatin accessibility of human monocytes has characteristic changes after typeinterferon stimulation and makes preparation for downstream gene expression.