Journal: Science Advances

Article Title: Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells

doi: 10.1126/sciadv.adf8549

Figure Lengend Snippet: ( A ) Left: Uniform manifold approximation and projection (UMAP) visualization of integrated transcriptomic and epigenetic profiling of lymphangioleiomyomatosis (LAM) lung. The integration included 12,361 cells from single-cell RNA sequencing (scRNA-seq) profiling and 10,050 nuclei from multiome and single-nucleus assay for transposase-accessible chromatin (snATAC) profiling. Cells/nuclei were colored by predicted cell types. Middle: UMAP visualization of cells/nuclei colored by data modalities and profiling methods. Right: Dot plot visualization of expression of representative genes differentially expressed in LAM CORE , including known LAM markers [Premelanosome Protein (PMEL), melan-A (MLANA), Vascular Endothelial Growth Factor D (VEGFD), Actin Alpha 2, Smooth Muscle (ACTA2)] and our predicted signature [HOXD11, ESR1, and pre–B cell leukemia homeobox 1 (PBX1)]. iMON, inflammatory monocytes; pMON, patrolling monocytes; IM, interstitial macrophage; AM, alveolar macrophage; AT1, alveolar type 1 cell; VEC, venous endothelial cell; CAP1, capillary cell 1; SVEC, systemic venous endothelial cell; AEC, arterial endothelial cell; VSMC, vascular smooth muscle; AF1, alveolar fibroblast 1; LEC, lymphatic endothelial cell; NK, natural killer; T reg , regulatory T cell. ( B ) Motifs enriched in the differentially accessible peaks (DAPs) in LAM CORE cells. ( C ) The expression levels of corresponding transcription factors (TFs) and genes are increased in LAM versus control lung. Pink, predicted signature genes enriched in LAM CORE cells; blue, genes not selectively expressed in LAM CORE , average expression levels (pseudo-bulk) were compared between LAM and control lung. ( D ) Gene ontology (GO) terms enriched by genes near (<10 kb) DAPs in LAM CORE cells. ( E ) Heatmap visualization of identified peak-to-gene (P2G) links ( y axis), which correlated ATAC accessibility and RNA expression patterns across cells ( x axis) in RNA and ATAC profiling of LAM. Labels on the right represent k -means clusters of P2G links. ( F ) P2G links in genomic regions of HOXA10 (left) and PBX1 (right). Tracks on the top left of each panel showed normalized ATAC accessibility in each cell type. Violin plots on the top right of each panel showed expression patterns of HOXA10 and PBX1 in each cell type. Scores of P2G links represent correlations of ATAC peak accessibility and RNA expression across cell types. bp, base pair.

Article Snippet: RNA and ATAC reads from 10x Multiome single-nucleus RNA (snRNA) and ATAC sequencing of the LAM lungs ( n = 2) were demultiplexed and processed using the Cell Ranger Analysis, Reconstruction, and Clustering (ARC) software package v 2.0.0 (10x Genomics) and human reference hg38.

Techniques: RNA Sequencing, Expressing, Control, RNA Expression

Journal: Hepatology Communications

Article Title: Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice

doi: 10.1097/HC9.0000000000000473

Figure Lengend Snippet: Single-nucleus RNA sequencing analysis revealed that myosin phosphatase target subunit 1 ablation contributes to the smooth muscle cell phenotype. (A) UMAP plot of all single-nucleus RNA sequencing data showing a total of 6 distinct cell types. (B) UMAP plot of all single-nucleus RNA sequencing data based on samples. Blue represents smooth muscle cells of KO mice. Orange represents smooth muscle cells of wild-type mice. (C) Percentage of cells in each subgroup. WT: control mice; KO: homozygous mice. Top enriched pathways for gene expression changes in cluster 1 (D) and cluster 6 (E). Abbreviations: ECM, extracellular matrix; KO, knockout; PKG, protein kinase G; UMAP, uniform manifold approximation and projection; WT, wild type.

Article Snippet: The authors also thank Singleron Biotechnologies (Nanjing, China) for providing single-nucleus RNA sequencing and Jiaxin Xiong for her assistance and technical support in data analysis.

Techniques: RNA Sequencing, Control, Gene Expression, Knock-Out