Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA.
View Article and Find Full Text PDFIn situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections.
View Article and Find Full Text PDFRecent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota.
View Article and Find Full Text PDFIn situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. Recently there has been a surge of multiplexed RNA in situ techniques but their application to human tissues and clinical biopsies has been limited due to their large size, general lower tissue quality and high background autofluorescence. Here we report DART-FISH, a versatile padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections at cellular resolution.
View Article and Find Full Text PDFUnderstanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations.
View Article and Find Full Text PDFHumans have a complicated symbiotic relationship with their gut microbiome, which is postulated to impact host health and disease broadly. Epigenetic alterations allow host cells to regulate gene expression without altering the DNA sequence. The gut microbiome, offering environmental hints, can influence responses to stimuli by host cells with modifications on their epigenome and gene expression.
View Article and Find Full Text PDFMicroRNAs (miRNAs), small non-coding RNAs approximately 20-25 nt in length, play important roles via directly binding to the corresponding 3' UTR of target mRNAs. Recent research has shown that miRNAs cover a wide range of diseases, including several types of cancer. It is interesting to note that miR-206 operates as a tumor suppressor and is downregulated in abundant cancer types, such as breast cancer, lung cancer, colorectal cancer, and so forth.
View Article and Find Full Text PDFDiabetes mellitus (DM) has been the most prevalent global metabolic disease, turning into a serious risk for human health. Several researches have recorded a role for inflammation and immunity in the pathogenesis of both in T1DM and in T2DM. Lots of chemical agents are available to control and to cure diabetic patients, which are not always sufficient for euglycemia maintenance and late stage diabetic complications avoidance.
View Article and Find Full Text PDFClassic approaches to mapping the developmental history of cells in vivo have relied on techniques that require complex interventions and often capture only a single trajectory or moment in time. We have previously described a developmental barcoding system to address these issues using synthetically induced mutations to record information about each cell's lineage in its genome. This system uses MARC1 mouse lines, which have multiple homing guide RNAs that each generate hundreds of mutant alleles and combine to produce an exponential diversity of barcodes.
View Article and Find Full Text PDFGenetic variations such as single nucleotide polymorphisms (SNPs) can cause susceptibility to cancer. Although thousands of genetic variants have been identified to be associated with different cancers, the molecular mechanisms of cancer remain unknown. There is not a particular dataset of relationships between cancer and SNPs, as a bipartite network, for computational analysis and prediction.
View Article and Find Full Text PDFKarst aquifers, capable of storing and transmitting large amount of water, are the main source of drinking water in many regions worldwide. Their excessive permeability leads to an enhanced vulnerability to retain and spread the contamination accordingly. From sustainability perspective, the environmental, economic and social impacts of karst contamination on water resources management are gaining more attention.
View Article and Find Full Text PDFBackground: Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific enzyme with the lowest enzymatic rate, which determines the overall rate of the other reactions in the pathway that converts ammonia to carbamoyl phosphate in the first step of the urea cycle. Carbamoyl phosphate synthetase 1 deficiency (CPS1D), which usually presents as lethal hyperammonemia, is a rare autosomal recessive hereditary disease.
Case: We report a case of a two-day-old female neonate with lethal hyperammonemia.