Project description:To dissect the early aspects of liver haematopoiesis as well as the development of other liver cell lineages we generated a new single cell RNA-seq (scRNA-seq) atlas of the mouse E12.5 liver
Project description:Haematopoiesis-specific Fh1 deletion causes lethal foetal liver haematopoietic defects. To understand the impact of Fh1 deletion on the transcriptome of foetal liver Lin- c-Kit+ cells we preformed microarray analysis. To conditionally delete Fh1 in the foetal liver we used the Vav-iCre recombinase and a Fh1 flox allele. Foetal livers were dissected and used to generate a single cell suspension. Lin- c-Kit+ cells were FACS sorted and lysed for total RNA preparation. We collected samples from 4 experimental animals (Fh1 fl/fl; Vav-iCre/+) and 3 control animals (Fh1 fl/fl).
Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions.
Project description:Liver disease alters the gut microenvironment by liver-gut axis. To investigate the composition and transcriptome changes of various intestinal cell populations in liver cirrhosis, we delineated a single-cell atlas of the colon from mice treated CCl4 for 6 weeks.
Project description:We perfomed single-cell RNA-sequnecing of around 10,000 cells from normal human liver tissue to construct a human liver cell atlas. We reveal previously unknown subtypes in different cell type compartments. We also use our normal liver cell atlas to infer perturbed phenoytpes of cells from HCC samples, human cells engrafted into a mouse liver and liver organoids.
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis represent distinct yet interconnected pathological processes underlying chronic liver disease progression. While high-fat diet (HFD)-induced MASH models recapitulate metabolic inflammation, carbon tetrachloride (CCl₄)-induced models capture toxicant-driven fibrogenesis. Here, we performed single-cell RNA sequencing (scRNA-seq) on liver tissues from HFD-induced MASH and CCl₄-induced fibrosis mouse models to construct a high-resolution atlas of liver cellular heterogeneity. This work establishes a valuable resource for dissecting liver disease mechanisms, enabling targeted therapeutic discovery and offering a framework for integrating diverse preclinical models of chronic liver injury.
Project description:The paralogous histone acetyltransferases KAT6A and KAT6B are large 200 kDa proteins of identical protein domain structure with high sequence similarity within the functional protein domains. Kat6a and Kat6b null mutation have severe effects on mouse embryonic and foetal development as well as on adult stem cell populations. Apart from the well-defined MYST family histone acetyltransferase domain, the proteins have N-terminal winged-helix domains followed by tandem plant homeodomain fingers preceding the histone acetyltransferase domain, as well as a long unstructured acidic region and serine and methionine rich regions following the histone acetyltransferase domain. In this study we examined the effects of point mutations that reduce the histone acetyltransferase function to background levels on gene expression in E9.5 mouse embryos and E14.5 mouse foetal liver haematopoietic cells and compared these to the effects of the null mutations of the Kat6a and Kat6b gene.