Project description:Chronic histiocytic intervillositis of unknown origin (CHI) is a rare placental disorder associated with adverse pregnancy outcomes, frequent recurrence, and a lack of effective preventive strategies. Recent insights indicate a potential link between CHI-associated inflammatory lesions and the inflammasome pathway, suggesting innovative therapeutic avenues. Here we show a potential role of the inflammasome pathway in CHI through comprehensive transcriptomic analysis of grade 2 or 3 histopathologic CHI samples, paired with placental controls. Additionally, we present case studies of three individuals with recurrent CHI, who have undergone treatment with anakinra and colchicine throughout pregnancy, resulting in improved perinatal outcomes. Notably, all cases are characterised by the birth of healthy, full-term infants, with reduced or absent intervillositis recurrence. Placental assessment unveils heightened activation of the NLRP3-PYCARD inflammasome pathway and IL-1β processing in CHI samples, with downregulation observed in treated pregnancy samples, devoid of intervillositis. Collectively, these findings suggest a potential therapeutic role for targeting the inflammasome pathway in preventing recurrent CHI in pregnant individuals
Project description:Capture Hi-C (CHi-C) is a state-of-the art method for profiling chromosomal interactions involving targeted regions of interest (such as gene promoters) globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model, and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments, in which many spatially dispersed regions are captured, such as in Promoter CHi-C. We implement these procedures in CHiCAGO (http://regulatorygenomicsgroup.org/chicago), an open-source package for robust interaction detection in CHi-C. We validate CHiCAGO by showing that promoter-interacting regions detected with this method are enriched for regulatory features and disease-associated SNPs.
Project description:Capture Hi-C (CHi-C) is a state-of-the art method for profiling chromosomal interactions involving targeted regions of interest (such as gene promoters) globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model, and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments, in which many spatially dispersed regions are captured, such as in Promoter CHi-C. We implement these procedures in CHiCAGO (http://regulatorygenomicsgroup.org/chicago), an open-source package for robust interaction detection in CHi-C. We validate CHiCAGO by showing that promoter-interacting regions detected with this method are enriched for regulatory features and disease-associated SNPs. Three human CHi-C biological replicates were generated (comprising 1, 2and 3 technical replicates). Two mouse CHi-C biological replicates were generated (both comprising three technical replicates) and a mouse Hi-C dataset. The publicly available HiCUP pipeline (doi: 10.12688/f1000research.7334.1) was used to process the raw sequencing reads. This pipeline was used to map the read pairs against the mouse (mm9) and human (hg19) genomes, to filter experimental artefacts (such as circularized reads and re-ligations), and to remove duplicate reads. For the CHi-C data, the resulting BAM files were processed into CHiCAGO input files, retaining only those read pairs that mapped, at least on one end, to a captured bait. CHiCAGO then identified Hi-C restriction fragments interacting, with statistical significant, to captured baits.
Project description:Genome organization influences transcriptional regulation by facilitating interactions between gene promoters and distal regulatory elements. To analyse distal promoter contacts we used Capture Hi-C (CHi-C) to enrich for promoter-interactions in a HiC lib
Project description:We report the application of H3K27me3 ChI-seq assays in hematopoietic stem and progenitors cells (HSPCs) from p53+/+ and p53R248W/+ mutant mice. We also performed RNA-seq assays to examine the impact of p53 on gene expression in hematopoietic stem and progenitor cells.
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post transcriptional control of several pathway intermediates, and essential for regulation in skeletal muscle of many species, such as mice, cattle, pig and so on. However, a little number of miRNAs have been reported in the muscle development of goat. In this study, the longissimus dorsi transcripts of goat at 1- and 10-month-old were analyzed for RNA-seq and miRNA-seq. The results showed that 10-month-old Longlin goat expressed 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the 1-month-old were founded. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in muscle fiber hypertrophy of goat were identified in 10-month-old Longlin and Nubian goat compared with 1-month-old. Five miRNA–mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA–mRNA negative correlation network analysis. Our results provided an insight into the functional roles of miRNAs of goat muscle-associated miRNAs, allowing us to better understand the transformation of miRNA roles during mammalian muscle development.
Project description:Genome organization influences transcriptional regulation by facilitating interactions between gene promoters and distal regulatory elements. To analyse distal promoter contacts mediated by the PRC1 complex we used Capture Hi-C (CHi-C) to enrich for promoter-interactions in a HiC library in Ring1a KO and Ring1a/b dKO mouse ES cells.
Project description:Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti- tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS) induced CRC mice model was established and the prevention effect of Camellia nitidissima Chi extracts on the evolving of CRC was evaluated by gross examination, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based metabolomics and correlation network analysis. The results showed that Camellia nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolism towards the normal state. Moreover, the butanol fraction showed a better efficiency than the water-soluble fraction of Camellia nitidissima Chi. The study pave the way for further development of Camellia nitidissima Chi extracts as a potent CRC inhibitor. In this work, rats were divided into control group, carcinoma group, and two drug groups of JHC and CNC. The acronyms JHC means the water-soluble fraction of Camellia nitidissima Chi. The acronyms CNC means the butanol fraction of Camellia nitidissima Chi.