MassIVE MSV000098058

Partial Public PXD064467

P21 plus Senescent Macrophages Fuel Inflammation and Disease in Aging and Metabolic Dysfunction-Associated Steatotic Liver Disease

Subscribe Comment Convert Spectra Add Reanalysis

Description

DNA damage or other cellular stress can lead to an irreversible cell cycle arrest, known as cellular senescence. While cellular senescence can be beneficial in some contexts such as wound healing and development, it is now recognized as a major source of sterile inflammation in aging tissues via the secretion of inflammatory factors known as the senescence-associated secretory phenotype (SASP). Targeting senescent cells is therefore an emerging strategy for treating age-related diseases, however, the identity and function of specific senescent cell types remain unclear. Here, we identify p21 plus senescent macrophages as a key source of chronic inflammation in aging and MASLD. To further investigate macrophage senescence, we developed an in vitro model of DNA damage-induced macrophage senescence, using primary mouse and human macrophages, which we leveraged to identify unique biomarkers that distinguish senescent macrophages from other established polarized states. We show that DNA damage or excess cholesterol induces stable macrophage senescence marked by an elevated SASP, mitochondrial dysfunction, and interferon signaling. These senescent macrophages accumulate in aged mouse livers, particularly in Kupffer cells, and are enriched in human cirrhotic liver tissue. Using transcriptomic profiling we identified a unique MSen signature to identify macrophage senescence both in vitro and in vivo in both mice and humans. We also showed that senescent macrophages can be selectively targeted for depletion using the senolytic ABT-263 (Navitoclax), which reduces liver steatosis and inflammation in MASLD models, highlighting macrophage senescence as a major source of inflammaging and promising therapeutic target in age-related diseases [doi:10.25345/C5445HR1K] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: senescence ; macrophages ; DIA-MS ; secretome ; SASP ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Birgit Schilling, Buck Institute, USA
Submitting User: cking
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.