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Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.
Pubmed ID: 36759512 RIS Download
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Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware package that implements and enhances circular visualization in R. Due to natural born feature of R to draw statistical graphics, this package can provide more general and flexible way to visualize huge information in circular style.
View all literature mentionsComputable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware package for functional analysis of sequences by classifying them into families and predicting presence of domains and sites. Scans sequences against InterPro's signatures. Characterizes nucleotide or protein function by matching it with models from several different databases. Used in large scale analysis of whole proteomes, genomes and metagenomes. Available as Web based version and standalone Perl version and SOAP Web Service.
View all literature mentionsService providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsSoftware package for DNA and protein sequence alignment to find regions of local or global similarity between Protein or DNA sequences, either by searching Protein or DNA databases, or by identifying local duplications within a sequence.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsSoftware as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.
View all literature mentionsSoftware R package for statistical analysis and visualization of functional profiles for genes and gene clusters.
View all literature mentionsSoftware tool to provide fast all in one preprocessing for FastQ files. Developed in C++ with multithreading supported to afford high performance. Performs quality control, adapter trimming, quality filtering, per read quality pruning and many other operations with a single scan of the FASTQ data.
View all literature mentionsCollection of publicly available data of curated receptors, ligands and their interactions. Integrates existing datasets that pertain to cellular communication and new manually reviewed information. Used to search for particular ligand or receptor or to interrogate single cell transcriptomics data.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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