Single-nucleus RNA-seq2 of liver tissue of 3 months old mice to investigate crosstalk between ploidy and zonation
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ABSTRACT:
PROVIDER: PRJEB39472 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4354530_1.fastq.gz | Fastqsanger.gz | |||
| ERR4354530_2.fastq.gz | Fastqsanger.gz | |||
| ERR4354540_1.fastq.gz | Fastqsanger.gz | |||
| ERR4354540_2.fastq.gz | Fastqsanger.gz | |||
| ERR4354550_1.fastq.gz | Fastqsanger.gz |
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Project description:Single-nucleus RNA-seq-2 method that allows deep characterization of nuclei isolated from frozen archived tissues. We have used this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy. This method has the potential to explore archived samples, in order to study the development and progression of disease in complex tissues. To illustrate the potential of this method, we have deeply characterized the cellular heterogeneity driven by spatial distribution and different levels of ploidy in the young adult mouse liver.
2021-05-06 | E-MTAB-9333 | biostudies-arrayexpress
Project description:Single-nucleus RNA-seq of liver tissue of 3 months old mice to investigate crosstalk between ploidy and zonation
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Project description:Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.
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Project description:Single-nucleus RNA-seq-2 method that allows deep characterization of nuclei isolated from frozen archived tissues. We have used this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy. This method has the potential to explore archived samples, for instance to study the development and progression of disease in complex tissues. To illustrate the potential of this method, we have deeply characterized the cellular heterogeneity driven by spatial distribution and different levels of ploidy in the young adult mouse liver.
2021-05-06 | E-MTAB-10223 | biostudies-arrayexpress
Project description:Whereas most eukaryotic cells are diploid, carrying two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, the consequences of altered ploidy for cellular gene expression remain poorly understood. We quantified changes in the transcriptome and proteome of the yeast Saccharomyces cerevisiae with different ploidy, from the haploid to the tetraploid state. We found that the abundance of proteins increases with ploidy, but does not scale proportionally with increasing DNA content, suggesting a compensatory, cellular response to increases in ploidy. We further found that pathways related to cytoplasmic ribosomes and translation are differentially regulated. With increasing ploidy the cells reduced the rRNA and ribosomal protein abundance, although they maintained a constant translational output. These adaptations stem from an active process that involves the kinases Tor1 and Sch9 and the transcriptional corepressor of rDNA transcription, Tup1. Consistent with our results in yeast, human tetraploid cells show reduced mTORC1 activity and downregulated their ribosome content via the Tup1 homolog Tle1, demonstrating that the proteome remodeling pathway discovered here constitutes a conserved response pathway to increased ploidy.
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Project description:While most eukaryotic cells are diploid, with two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, a complete picture of consequences of altered ploidy is missing. We analyzed transcriptome and proteome changes in budding yeast Saccharomyces cerevisiae from haploid to tetraploid and found that the mRNA and protein abundance increases linearly with ploidy, but does not double with doubling the DNA content. Besides this linear increase, we found that pathways related to mitochondria and to cytoplasmic ribosomes and translation are differentially regulated. Indeed, with increasing ploidy the cells reduce mitochondrial content and this effect can be rescued by antioxidants. Moreover, cells of higher ploidy reduce their ribosome content while maintaining constant translational output. We show that this is an active process regulated via the Tor1 and Sch9 kinases and a transcriptional corepressor of rDNA transcription, Tup1. Similarly, human tetraploid cells downregulate their ribosome content via Tle1, a Tup1 homolog, demonstrating that the proteome remodeling is a conserved response to increased ploidy.
2022-08-15 | PXD022605 | Pride
Project description:Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms, and can serve adaptive functions to specialized, somatic cells in multicellular organisms (Edgar & Orr-Weaver, 2001; Orr-Weaver, 2015; Van De Peer et al., 2017). However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation (Andalis et al., 2004; Fujiwara et al., 2005). To understand the physiological challenges that suddenly-increased chromosome content imposes on cells, we used S. cerevisiae cells to ask how much chromosomal DNA cells may contain, and what determines this limit. We generated polyploid cells using two distinct methods causing cells to undergo endoreplication and identified the maximum ploidy of these cells, 32-64C. We found that physical determinants that alleviate or exacerbate cell surface stress increase and decrease the limit to ploidy, respectively. We also used these cells to investigate gene expression changes associated with increased ploidy, and identified the repression of genes involved in ergosterol biosynthesis. We propose that ploidy is inherently limited by the impacts of growth in size, which accompany whole genome duplication, to cell surface integrity.
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Project description:Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal hepatic function. Wnt signaling is a master regulator of spatial liver zonation. A perivenous-periportal Wnt activity gradient orchestrates metabolic zonation by activating genes in perivenous hepatocytes, while suppressing genes in their periportal counterparts. The understanding of liver gene zonation and zonation regulators in disease was limited. Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fat accumulation, inflammation, and fibrosis. Here, we investigated the perturbation of liver gene zonation in a mouse NASH model by combination of spatial transcriptomics, bulk RNAseq and in situ hybridization. Wnt target genes represented a major subset of genes showing altered spatial expression in the NASH liver. The altered Wnt target gene expression level and zonation spatial pattern were in line with the upregulation of Wnt regulators and the augmentation of Wnt signaling. Particularly, we found that the Wnt activator Rspo3 expression was restricted to the perivenous zone in control livers, whereas expanded to the periportal zone in NASH livers. AAV8-mediated RSPO3 overexpression in controls resulted in a zonation change, and further amplified the disturbed zonation of Wnt target genes in NASH, but had no impacts on steatosis, inflammation and fibrosis. In summary, our study demonstrated the alteration of Wnt signaling in a mouse NASH model, leading to perturbed liver zonation.
2024-08-01 | GSE248077 | GEO
Project description:Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/beta-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/beta-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/beta-catenin. The glucagon and Wnt/beta-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counter play with the Wnt/beta-catenin signaling pathway.
2018-03-01 | GSE110673 | GEO
Project description:Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/beta-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/beta-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/beta-catenin. The glucagon and Wnt/beta-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counter play with the Wnt/beta-catenin signaling pathway.
2018-03-01 | GSE110672 | GEO