Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dynamic human liver proteome atlas reveals functional insights into disease pathways

ABSTRACT: Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell-type resolution. Here, we quantify more than 10,000 proteins and 150,000 sequence-unique peptides across total liver, the major liver cell types, time-course of primary cell cultures and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serves as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver biopsies include signatures of stellate cell activation resembling liver cirrhosis, providing functional insights.

INSTRUMENT(S): Q Exactive HF-X, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kupffer Cell, Endothelial Cell Of Sinusoid, Primary Cell, Hepatocyte, Hepatic Stellate Cell, Liver, Cell Culture

DISEASE(S): Non-alcoholic Steatohepatitis,Liver Cirrhosis

SUBMITTER: Lili Niu

LAB HEAD: Matthias Mann

PROVIDER: PXD027722 | Pride | 2022-05-08

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

HEK293T_The Label-free DIA-MS nanoproteomics workflow based on empirically corrected spectral library and application for 5000 PBMCs stimulated by LPS

Project description:A refined HEK293T peptide dilution series acquired in DIA mode on Orbitrap Lumos.

2022-04-27 | PXD029738 | Pride

Deletion of GSE1 and HDAC1 inactivation alters proteomic profiles and cell cycle control

Project description:The DNA damage response (DDR) is orchestrated by multiple, tightly regulated signalling events. We discovered that genetic suppressor element 1 (GSE1) forms a complex with the histone deacetylation 1 (HDAC1) / CoREST complex and that loss of GSE1 hampers DDR induction. To investigate how GSE1 and HDAC1 can regulate DDR and whether their mode of action might be overlapping, we performed a proteomic analysis using quantitative mass spectrometry based on the TMTpro 16-plex isobaric labelling technology (Li et al., 2020). We determined global acetylome and phosphorylome profiles in the nearly haploid human cell line HAP1 (Andersson et al, 1987) using WT, GSE1 KO and HDAC1 CI backgrounds and compared patterns between untreated and etoposide-treated (0.1 µM, 6 hrs) cells.

2023-10-23 | PXD040339 | Pride

Maternal hyperglycemia induces alterations in hepatic amino acid, glucose and lipid metabolism of neonatal offspring: Multi-omics insights from a diabetic pig model

Project description:Intrauterine exposure to disturbed maternal glucose metabolism is associated with adverse consequences for the offspring. Hepatic disorders in affected offspring emerge in early development; thus, detection of disease biomarkers at an early stage may elucidate the underlying mechanisms of maternal hyperglycemia-induced metabolic disease and improve timely diagnosis and treatment strategies. To systematically study the molecular consequences of maternal hyperglycemia, we used data independent acquisition (DIA) proteomics and compared the molecular profiles of liver of three days old wild-type piglets born to a transgenic hyperglycemic pig model with those of wild-type piglets born to normoglycemic mothers.

2023-07-10 | PXD040305 | Pride

Transcription profiling of human hepatic and pancreatic stellate cells obtained from tissues of chronic inflammation, and primary or metastatic cancers

Project description:Differences in the expression profile of hepatic and pancreatic stellate cells are investigated. Aim is to identify organ and disease specific transcriptome signatures of stellate cells, comparing hepatic and pancreatic stellate cells obtained from tissues of chronic inflammation, and primary or metastatic cancers of the pancreas. Tissues of chronic pancreatitis (n=6), pancreatic ductal adenocarcinoma (n=5), liver cirrhosis (n=5) and liver metastasis of pancreatic ductal adenocarcinoma (n=6) were collected and stellate cells were isolated by the outgrowth method. Using cDNA microarrays, differentially expressed genes are identified.

2010-01-15 | E-TABM-625 | biostudies-arrayexpress

15 cm Aurora Gen3 column benchmarking on an Exploris 480

Project description:A comprehensive proteome map is essential to elucidate molecular pathways and protein functions. Although great improvements in sample preparation, instrumentation and data analysis already yield-ed impressive results, current studies suffer from a limited proteomic depth and dynamic range there-fore lacking low abundant or highly hydrophobic proteins. Here, we combine and benchmark advanced micro pillar array columns (µPAC) operated at nanoflow with Wide Window Acquisition (WWA) and the AI-based CHIMERYS search engine for data analysis to maximize chromatographic separation power, sensitivity and proteome coverage. Our data shows that µPAC columns clearly outperform classical packed bed columns boosting peptide IDs by up to 50% and protein IDs by up to 24%. Using the above-mentioned analysis platform, more than 10,000 proteins could be identified from a single 2 h gradient shotgun analysis for a triple proteome mix of human, yeast and E. coli digests. At high sample loads of 400 ng all three uPAC types yielded comparable number of protein identifications, whereas the 50cm neo column performed best when lower inputs of less than 200 ng were injected. This additional dataset comprises additional data generated with the Aurora Elite G3 column (150 mm x 75 µm, 1.7 µm, IonOpticks) for comparison to the aforementioned µPAC technology.

2024-02-13 | PXD045457 | Pride

SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage

Project description:Quantification of Spike cleavage across different Sars-Cov2 variants by partial reaction monitoring mass spectrometry

2022-02-22 | PXD027641 | Pride

PBMC_A data-independent acquisition (DIA)-based quantification workflow for proteome analysis of 5000 cells

Project description:An optimized workflow for nanoscale proteomics is applied to the proteomics profiling of 5000 PBMCs in DIA mode on Orbitrap Lumos.

2022-04-27 | PXD029721 | Pride

A common gene signature of the right ventricle in failing rat and human hearts

Project description:The molecular mechanisms of progressive right heart failure are incompletely understood. We systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signatures, protein, and transcription factor networks specific to ventricles and compensated or decompensated disease states. Proteomic and RNA-FISH analyses confirmed PAB-mediated regulation of key genes (including proenkephalin) and revealed spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with transcriptome data sets from human patients with chronic thromboembolic pulmonary hypertension led to the identification of more than 50 genes whose expression levels correlated with the severity of right heart disease, including multiple matrix-regulating and secreted factors. These data define a conserved, differentially regulated genetic network associated with right heart failure in rats and humans

2024-04-11 | PXD047022 | Pride

Cellular, molecular and proteomic characteristics of early Hepatocellular carcinoma

Project description:Ηepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early de-tection/diagnosis is vital for the prognosis of HCC whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on patient’s 6 month surveillance and use of at least two imaging modalities. The aim of this study was to investigate diagnostic markers for the detection of early HCC based on proteome analysis, microRNAs (miRNAs) and circulat-ing tumor cells (CTCs) in the blood of patients with cirrhosis, early and advanced HCC. We studied 89 patients with HCC of whom 33 had early HCC and 28 cirrhotic patients. CTCs were detected by Real-Time Quantitative Reverse Transcription PCR and immunofluorescence using the markers Epithelial cell adhesion molecule (EPCAM), Vimentin, A Fetoprotein (AFP) and surface major Vault protein (sMVP). Expression of the five most commonly HCC-involved miRNAs (miR-122, miR-200a, miR-200b, miR-221, miR-222) was examined in the serum by qRT-PCR. Finally patient serum was analyzed by whole proteome analysis (LC/MS). Twenty seven out of 53 (51%) patients with advanced HCC had detectable CTCs. Among them, 10/27 (37%) presented evidence of mesenchymal or intermediate stage cells (vimentin and/or sMVP positive). Moreover, 5/17 (29%) patients with early HCC and 6/28 (21%) cirrhotic patients had detectable CTCs. Patients with early and advanced HCC exhibited a significant increase of miR-200b when compared to cirrhotic patients. Our proteome analysis indicated that early HCC patients present a significant upregulation of APOA2, APOC3 proteins when compared to cir-rhotic patients, that when used in combination, cover the 100% of the patients with early HCC. In conclusion, miR-200b, APOA2 and APOC3 proteins are sensitive markers and can be poten-tially useful in combination for the early diagnosis of HCC.

2023-03-11 | PXD033306 | Pride

Adipogenic characterization of immortalized CD55+ progenitor cells frAdipogenic characterization of immortalized CD55+ progenitor cells from human white adipose tissueom human white adipose tissue

Project description:Background: Mature adipocytes are notoriously difficult to study ex vivo and alternative cell culture systems have therefore been developed. One of the most common models are human adipose progenitor cells (hAPCs). Unfortunately, these display replicative senescence after prolonged culture conditions, which limits their use in mechanistic studies. Methods: Herein, we knocked in human telomerase reverse transcriptase (TERT) into the AAVS1 locus of CD55+ hAPCs derived from abdominal subcutaneous adipose tissue and characterized the cells before and after differentiation into adipocytes. Results: Immortalized TERT-hAPCs retained proliferative and adipogenic capacities comparable to those of early-passage wild type hAPCs for >80 passages. In line with this, our integrative transcriptomic and proteomic analyses revealed that TERT-hAPCs displayed robust adipocyte expression profiles. This was confirmed by functional analyses of lipid turnover where TERT-hAPCs exhibited pronounced responses to insulin and pro-lipolytic stimuli such as isoprenaline, dibutyrul cAMP and tumor necrosis factor alpha. In addition, TERT-hAPCs could be readily cultured in both standard 2D and 3D-cultures and proteomic analyses revealed that the spheroid culture conditions improved adipogenesis. Conclusion: Through descriptive and functional studies, we demonstrate that immortalization of human CD55+ hAPCs is feasible and results in cells with stable proliferative and adipogenic capacities over multiple passages. As these cells are cryopreservable, they provide the additional advantage over primary cells of allowing repeated studies in both 2D and 3D model systems with the same genetic background.

2024-01-17 | PXD043293 | Pride

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