Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

ABSTRACT: Reconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology. Additional data to reproduce the data presented in this study with instrctions can be found at https://github.com/almaan/ST-mLiver and https://zenodo.org/record/4399655

ORGANISM(S): Mus musculus

PROVIDER: GSE165141 | GEO | 2021/01/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Liver zonation patterns and cell size variability in isolated human hepatocytes

Project description:Human hepatocytes differ in gene expression and function across the hexagonal lobules of the tissue microarchitecture, a phenomenon referred to as liver zonation. Hepatocytes also display intra-lobular differences in cell size, but to what extent zonal expression and function correlate with cell size in isolated human hepatocytes is not entirely clear. Here, we first used our accumulated experience of nearly 100 hepatocyte isolations to assess the impact of donor background and process parameters on hepatocyte quality. We observed substantial inter-batch variability in cell size distributions and a tendency for overall cell size to affect the outcome of hepatocyte isolation and cryopreservation. We further separated cells into different size fractions and analyzed them with label-free quantitative proteomics. This showed that protein abundances in different hepatocyte size fractions recapitulated the in vivo expression patterns of well-known zonal markers. We also found that proteins with sequential enrichment across fractions largely represented biological processes with known zonal specificity. This was confirmed by differences in the metabolic activity of zonated CYP enzymes. Altogether, our results show that hepatocyte size corresponds to zonal origin, and that our size fractionation approach can be used to study zone-specific liver functions in vitro.

2021-01-26 | PXD013142 | Pride

A spatially resolved single cell genomic atlas of the adult human breast [scRNA_cells]

Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.

2023-06-29 | GSE235326 | GEO

A spatially resolved single cell genomic atlas of the adult human breast [snRNA_nuclei]

2023-06-29 | GSE234817 | GEO

A spatially resolved single cell genomic atlas of the adult human breast [visium]

2023-06-29 | GSE234814 | GEO

Single-nucleus RNA-seq2 of liver tissue of 3 months old mice to investigate crosstalk between ploidy and zonation

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

Single-nucleus RNA-seq of liver tissue of 3 months old mice to investigate crosstalk between ploidy and zonation

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

A cell atlas of the regenerating human liver after portal vein embolization

Project description:In this work, we applied single-cell transcriptome sequencing on primary human liver tissue samples to study cellular processes underlying human liver regeneration. In order to study regeneration-specific cellular processes we obtained primary healthy liver tissue samples and liver tissue samples from patients that underwent a preoperative medical procedure called portal vein embolization (PVE). This medical treatment is performed to enlarge part of the liver such that a diseased portion can be removed avoiding liver insufficiency and thus we used post-PVE-derived tissues as a model to study liver regeneration in humans. This paradigm enabled us to catalog cell states related to tissue structure in two important and physiologically relevant conditions: hypertrophy and atrophy. In addition, we overcame technical challenges and provided novel protocols and pipelines for generating high quality liver cell atlases from frozen specimens showing consistency in results between fresh and frozen tissue datasets. Moreover, we established tissue-scale iterative indirect immunofluorescence imaging to enable high-dimensional spatial analysis of perivascular microenvironments and uncover cellular and histological alterations to regenerating liver lobules.

2024-04-13 | E-MTAB-12594 | biostudies-arrayexpress

Glucagon contributes to liver zonation in mice [Gcg infusion]

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

Glucagon contributes to liver zonation in mice [Gcg KO]

2018-03-01 | GSE110672 | GEO

Breast tissue regeneration is driven by cell-matrix interactions that coordinate multi-lineage stem cell differentiation through DDR1

Project description:Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in storm tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure and functions. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through the collagen receptor DDR1. DDR1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells to differentiate and form lobules via Notch signaling. These findings demonstrate how human breast tissue regeneration is triggered by transmission of signals from the extracellular matrix through an epithelial bilayer to coordinate structural changes that form a complex ductal-lobular network. More broadly, these findings suggest that DDR1 may coordinate collagen and Notch signaling to regulate multi-lineage differentiation and morphogenesis across diverse tissues.

2021-10-25 | GSE162296 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data