Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative characterization of the aging intestine secretome reveals novel secreted proteins that act in the extracellular space to regulate lifespan

ABSTRACT: Secreted proteins are essential to modulate the extracellular space and communicate to distal cells or tissues. But the importance of extracellular proteins in aging has been understudied. Here we use proximity labeling followed by quantitative proteomics to systematically characterize the intestine and neuron secretome in C. elegans. We identify many previously unknown intestine secreted proteins that change with age, and we validate the secretion of these proteins by in vivo cell biology. One of these secreted proteins, ACP7, is well conserved in humans. Overexpressing ACP7 extends lifespan in a secretion-dependent manner, and we find that ACP7 acts as a phosphatase in the extracellular space. Finally, we identify additional proteins along the secretion pathway that regulate lifespan, including VAPA – a protein localized to small secretory vesicles in the intestine. Our systematic characterization of tissue-specific secretome during aging uncovers novel proteins that impact lifespan and highlights the role of extracellular enzymes in aging.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE307266 | GEO | 2026/06/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Silencing SMOC2 protects from kidney fibrosis by inhibiting Fibroblast to Myofibroblast Transformation

Project description:Secreted MOdular Calcium-binding protein-2 (SMOC2) belongs to the SPARC (Secreted Protein Acidic and Rich in Cysteines) family of matricellular proteins whose members are known for their secretion into the extracellular space to modulate cell-cell and cel

2017-07-31 | GSE85209 | GEO

DsbA plays a critical and multi-faceted role in the production of secreted virulence factors by Erwinia carotovora

Project description:Erwinia carotovora subsp. atroseptica (Eca) is an enterobacterial phytopathogen causing economically-significant soft rot disease. Pathogenesis is mediated by multiple secreted virulence factors, many of which are secreted by the Type II (Out) secretion system. DsbA catalyses the introduction of disulphide bonds into periplasmic and secreted proteins. In this study, the extracellular proteome (secretome) of wild type Eca SCRI1043 and dsbA and out mutants was analysed by spectral counting mass spectrometry. This revealed that dsbA inactivation had a huge impact on the secretome and identified diverse DsbA- and Out-dependent secreted proteins, representing known, predicted and novel candidate virulence factors. Further characterisation of the dsbA mutant showed that secreted enzyme activities, motility, production of the quorum sensing signal and virulence were absent or greatly reduced. The impact of DsbA on secreted virulence factor production was mediated at multiple levels, including impacting on the Out secretion system and the virulence gene regulatory network. Transcriptome analyses revealed that the abundance of a broad, but defined, set of transcripts, including many virulence factors, was altered in the dsbA mutant, identifying a new virulence regulon responsive to extracytoplasmic conditions. In conclusion, DsbA plays a crucial, multi-faceted role in the pathogenesis of Eca. Keywords: Mutant comparison RNA samples used for genome-wide transcriptional profiling using microarrays: RNA was hybridised to four Eca genomic arrays, with each array hybridising one wild type and one dsbA mutant sample (from four independent cultures of each strain) and incorporating a dye-swap (i.e. wild type labelled with Cy3 in 2/4 and with Cy5 in 2/4).

2010-06-20 | E-GEOD-10647 | biostudies-arrayexpress

UNASSAMBLED CELL WALL PROTEINS FORM AGGREGATES IN THE EXTRACELLULAR SPACE OF CHLAMYDOMONAS REINHARDTII STRAIN UVM4

Project description:The green microalga Chlamydomonas reinhardtii is emerging as a promising cell biofactory for secreted recombinant protein (RP) production. In recent years, the generation of the broadly-used cell wall-deficient mutant strain UVM4 has allowed for a drastic increase in secreted RP yields. However, purification of secreted RPs from the extracellular space of C. reinhardtii strain UVM4 is challenging. Previous studies suggest that secreted RPs are trapped in a matrix of cell wall protein aggregates populating the secretome of strain UVM4, making it difficult to isolate and purify the RPs. To better understand the nature and behaviour of these extracellular protein aggregates, we analysed and compared the extracellular proteome of the strain UVM4 to its cell-walled ancestor, C. reinhardtii strain 137c. When grown under the same conditions, strain UVM4 produced a unique extracellular proteomic profile, including a higher abundance of secreted cell wall glycoproteins. Further characterization of high molecular weight extracellular protein aggregates in strain UVM4 revealed that they are largely comprised of pherophorins, a specific class of cell wall glycoproteins. Our results offer important new insights into the extracellular space of strain UVM4, including strain-specific secreted cell wall proteins and the composition of the aggregates possibly related to impaired RP purification. The discovery of pherophorins as a major component of extracellular protein aggregates will inform future strategies to remove or prevent aggregate formation, enhance purification of secreted RPs, and improve yields of recombinant biopharmaceuticals in this emerging cell biofactory.

2022-08-11 | PXD032195 | Pride

Reactive oxygen species (ROS) production activates unconventional secretion of antioxidant proteins

Project description:Signal-sequence-lacking superoxide dismutase 1 (SOD1) is secreted upon nutrient starvation, but the physiological relevance of this secretion is unclear. We now report that secreted SOD1 is functionally active. In addition, a secretome analysis has revealed number of other secreted cytoplasmic antioxidant enzymes, including both thioredoxins, (Trx1 and Trx2), and the peroxiredoxin Ahp1. Our data reveal that starvation triggers increased mitochondrial activity, leading to increased production of reactive oxygen species (ROS). Inhibiting mitochondrial activity or ROS, inhibited secretion of the antioxidants. We suggest elevated ROS that evade cytoplasmic antioxidants, can permeate across the plasma membrane to the extracellular space. Cells secrete antioxidants to prevent ROS-mediated damage to the extracellular space. These findings thus provide an understanding of why cells secrete signal sequence lacking proteins like SOD1 and the larger family of antioxidants.

2019-05-14 | PXD010849 | Pride

DsbA plays a critical and multi-faceted role in the production of secreted virulence factors by Erwinia carotovora

2008-08-26 | GSE10647 | GEO

Control of secreted protein gene expression and the mammalian secretome by the metabolic regulator PGC-1a

Project description:Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1α, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1α down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts (MEFs).

2016-12-01 | GSE87100 | GEO

A secretome CRISPR screen identifies SFRP1 as a regulator of epidermal self-renewal [ATAC-seq]

Project description:Secreted epidermal proteins play pivotal roles in cell-cell communication, extracellular matrix remodeling, and antimicrobial defense. However, the complete spectrum of secreted proteins in the epidermis has not been experimentally defined. In this study, we performed mass spectrometry on conditioned media from primary human keratinocytes, identifying 406 proteins that constitute the keratinocyte secretome. To assess functional impacts of uncharacterized secreted proteins on epidermal stem cell behavior, we devised a colony formation assay-based CRISPR screen. The screen identified six candidate proteins that promoted proliferation of epidermal progenitors and two proteins that inhibited it. Secreted frizzled related protein-1 (SFRP1), an inhibitor of Wnt signaling, was the most potent inhibitor of progenitor proliferation in the screen. We discovered that in addition to regulating Wnt activity, SFRP1 restrained epidermal stem cell proliferation by inhibiting ectopic expression of leukemia inhibitory factor (LIF). Collectively, our study defines the keratinocyte secretome, demonstrates the application of a CRISPR screen to assess the function of non-cell autonomous factors, and highlights SFRP1’s role in regulating epidermal balance.

2025-04-30 | GSE269626 | GEO

A secretome CRISPR screen identifies SFRP1 as a regulator of epidermal self-renewal [RNA-seq]

2025-04-30 | GSE269627 | GEO

A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts

Project description:Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of protein secretion. Specific in-vivo labeling of miCF proteins via biotin ligase TurboID using the POSTN promotor mirrors the in-vitro data. In summary, we identify numerous paracrine factors specifically secreted from CF in mice and humans. This secretome atlas may lead to new biomarkers and/or therapeutic targets for the activated CF.

2025-03-27 | GSE293090 | GEO

Nanonets collect cancer secretome from pericellular space

Project description:Identifying novel cancer biomarkers is important for early cancer detection as it can reduce mortality rates. The cancer sectretome, the collection of all macromolecules secreted by a tumor cell, alters its composition compared to normal tissue, and this change plays an important role in the observation of cancer progression. The collection and accurate analysis of cancer secretomes could lead to the discovery of novel biomarkers, thus improving outcomes of cancer treatment. We unexpectedly discovered that enzyme-instructed self-assembly (EISA) of a D-peptide hydrogelator results in nanonets/hydrogel around cancer cells that overexpress ectophosphatases. Here we show that these nanonets are able to rapidly collect proteins in the pericellular space (i.e., near the surface) of cancer cells. Because the secretory substances are at their highest concentration near the cell surface, the use of pericellular nanonets to collect the cancer secretome maximizes the yield and quality of samples, reduces pre-analytical variations, and allows the dynamic profiling of secretome samples. Thus, this new approach has great potential in identifying the heterotypic signaling in tumor microenvironments thereby improving the understanding of tumor microenvironments and accelerating the discovery of potential biomarkers in cancer biology.

2016-04-27 | PXD003924 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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