Secretome of Bone Marrow Stroma-Derived Neural Progenitor Cells: Proteomic Analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE13242 | GEO | 2008/10/18
SECONDARY ACCESSION(S): PRJNA109517
REPOSITORIES: GEO
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Project description:The Skeletal muscle is a metabolic active tissue that secretes various proteins. These so called myokines act auto-, para- and endocrine affecting muscle physiology and exert systemic effects on other tissues and organs. Myokines are also described to play a crucial role in the pathophysiology of metabolic diseases. Combining three different mass spectrometry based non-targeted and one antibody based targeted approach we investigated the secretome of differentiated primary human skeletal muscle cells derived from adult donors. A total of 548 non-redundant proteins were detected by combined proteomic profiling. Expression was confirmed on mRNA level for 501. Stringent consecutive filtering recruiting several database, i.e. SignalP, SecretomeP and ER_retention signals, the computational analysis assigned 306 as secretory proteins including 33 potentially novel myokines. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and further highlights the pivotal role of myokines in the regulation of multiple biological processes. We performed gene expression microarray analysis of primary human myotubes derived from twelve healthy individuals
2013-12-03 | E-GEOD-45473 | biostudies-arrayexpress
Project description:Recent evidence shows that adult hippocampal neural stem and progenitor cells (NSPCs) secrete a variety of proteins that affect tissue function. Though several individual NSPC-derived proteins have been shown to impact cellular processes like neuronal maturation and stem cell maintenance, a broad characterization of NSPC-secreted factors is lacking. Secretome profiling of low abundance stem cell populations is typically achieved via proteomic characterization of in vitro, isolated cells. Here, we analyzed the in vitro NSPC secretome using conditioned media from cultured adult mouse hippocampal NSPCs and detected over 200 different bioactive proteins with an antibody array. We next assessed the NSPC secretome on a transcriptional level with RNA sequencing (RNAseq) of cultured NSPCs. This comparison revealed that quantification of gene expression did not accurately predict relative protein abundance for several factors. Furthermore, comparing our transcriptional data with previously published single cell RNA sequencing datasets of freshly isolated hippocampal NSPCs, we found key differences in gene expression of secreted proteins between cultured and acutely isolated NSPCs. Understanding the components and functions of the NSPC secretome is essential to understanding how these cells may modulate the hippocampal neurogenic niche, as well as how they can be applied therapeutically. Cumulatively, our data emphasize the importance of using proteomic analysis in conjunction with transcriptomic studies and highlights the need for better methods of global unbiased secretome profiling.
2020-02-13 | GSE138381 | GEO
Project description:Desmoplastic small round cell tumor (DSRCT) is an aggressive malignancy that occurs predominantly in young adult males and is characterized by abdominopelvic sarcomatosis exhibiting multi-lineage cellular nests of epithelial, muscular, mesenchymal, and neural differentiation admixed with desmoplastic stroma. Prior to the recognition of the disease as a distinct clinical entity, DSRCT was invariably misclassified as poorly differentiated atypical cancer of the testes, ovary, mesentery, or gastrointestinal tract, and the chemotherapies used for those malignancies elicited poor clinical response. As previously reported, a tectonic shift in the treatment of these patients occurred after researchers made two astute observations: 1) DSRCT microscopically resembles other small round “blue cell” sarcoma subtypes (e.g., ES, rhabdomyosarcoma, synovial sarcoma), and 2) DSRCT and ES have the same N-terminal EWSR1 fusion partner. Proteomic analysis using a reverse-phase protein lysate array (RPPA) was used to elucidate biomarkers that distinguish DSRCT from adjacent normal tissue and Ewing sarcoma. This proteomic analysis revealed novel proteins, such as the androgen receptor and Syk, that may be susceptible to drug targeting, as well as oncogenic pathways like Akt-PI3K that are highly expressed in DSRCT.
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Project description:Cyclic regeneration of the endometrium, and its repair after parturition or injury, are crucial for successful reproduction. Mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSC) facilitate tissue repair via their secretome, which contains growth factors and cytokines that promote wound healing. Despite the implication of MSCs in endometrial regeneration and repair, the mechanisms remain unclear. This study tested the hypothesis that the secretome of MSCs from human BM upregulates human endometrial stromal cell (HESC) proliferation, migration and invasion, and activates pathways to increase HESC motility. MSCs were purchased from ATCC (BM-MSC-1) and cultured from the BM aspirate of a healthy female donor (BM-MSC-2). Indirect co-culture of MSCs and hTERT-immortalized HESCs via a transwell system studied the effect of the BM-MSC secretome on HESC proliferation, migration, and invasion. To study the effect of the MSC secretome on HESC gene expression, HESCs were exposed to the BM-MSC secretome via indirect co-culture for 24 h. Total RNA was extracted from HESCs for RNA sequencing (RNA-Seq). Differentially expressed genes (DEG) and significantly altered pathways were identified. Indirect co-culture of HESCs with BM- MSCs resulted in significant increase in HESC migration and invasion regardless of the source of MSCs. Effects on cellular proliferation varied among the BM-MSC source. Exposure of HESCs to the secretome of BM-MSCs changed the expression of 10,141 genes with FDR < 0.05. There was overlap among 4351 genes between HESCs exposed to BM-MSC-1 and BM-MSC-2, including upregulated expression of cell motility genes common to both BM-MSC exposures. Increased HESC motility by the secretome of BM-MSC appears to be mediated by paracrine and autocrine mechanisms, in part by modifying HESC gene expression. These data support the potential for leveraging the MSC secretome as a novel cell-free therapy in the treatment of disorders of endometrial regeneration.
2024-06-12 | GSE217506 | GEO
Project description:The Skeletal muscle is a metabolic active tissue that secretes various proteins. These so called myokines act auto-, para- and endocrine affecting muscle physiology and exert systemic effects on other tissues and organs. Myokines are also described to play a crucial role in the pathophysiology of metabolic diseases. Combining three different mass spectrometry based non-targeted and one antibody based targeted approach we investigated the secretome of differentiated primary human skeletal muscle cells derived from adult donors. A total of 548 non-redundant proteins were detected by combined proteomic profiling. Expression was confirmed on mRNA level for 501. Stringent consecutive filtering recruiting several database, i.e. SignalP, SecretomeP and ER_retention signals, the computational analysis assigned 306 as secretory proteins including 33 potentially novel myokines. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and further highlights the pivotal role of myokines in the regulation of multiple biological processes.
2013-12-03 | GSE45473 | GEO
Project description:Parkinson’s disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the wide array of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4 and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome potentiated the histological recovery of DA neurons, when compared to transplantation of hBMSCs themselves, a fact that probably explains the improved behavioral performance of secretome-injected animals in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete a variety of important exosome-related molecules such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.
2020-03-19 | PXD014887 | Pride
Project description:Human satellite cells were isolated from muscle biopsies and expanded in vitro. Cells were induced to differentiate into branched multinucleated myotubes by serum depletion and were harvested from three independent cultures after 72 hours. Total RNA was isolated, amplified, labelled and hybridised to Illumina Human WG-6v3 arrays. Data were analysed to identify a "virtual secretome". These data and proteomic data from similar cultures suggested that differentiating muscle cultures produce microvesicles - which were characterised in the ensuing experiment. Human satellite cells were cultured as before (duplicate cultures) and culture supernatants were subjected to a differential centrifugation procedure, resulting in isolation of two distinct vesicle populations: exosomes and microparticles. Total RNA was isolated from these vesicle populations and the cells from which they were derived. RNA was amplified, labelled and hybridised to Illumina Human HT12v3 arrays. Data from myotubes, exosomes and microparticles were analysed to identify transcripts present, differential expression and functional interpretation of transcriptomes. IDAT files are available on the ArrayExpress ftp site in the additional.zip file.
2011-04-30 | E-MTAB-423 | biostudies-arrayexpress
Project description:Secretome of Bone Marrow Stroma-Derived Neural Progenitor Cells: Proteomic Analysis
| PRJNA109517 | ENA
Project description:LYN kinase is a tyrosine kinase, that regulates cellular homeostasis in a context specific manner. Our group could show, that its expression in the leukemic microenvironment of chronic lymphocytic leukemia contributes to disease progression (Nguyen PH et al.; Cancer Cell; 2016). To analyze the effect of LYN kinase on the leukemia supportive phenotype of the bone marrow stromal cell line HS-5, we generated single cell clones of LYN deficient cells. These cells were analyzed in a Multi-Omic approach, including quantitative, label-free proteomic analysis of the Secretome.
2023-05-10 | PXD028855 | Pride
Project description:Protein secretion can mediate communication of distant cells in a multicellular organism and can control a broad range of physiological functions. Regulation of this process is crucial, especially for cells of the immune system that sense pathogens through specific receptors and release proteins that initiate and orchestrate the immune response. This secretome is today analyzed using antibody-based assays, but mass spectrometry could provide an unbiased and comprehensive alternative. Here we developed a quantitative, high resolution mass spectrometric workflow to detect and quantify proteins that are released from macrophages upon Toll-like receptor 4 (TLR4) activation by the microbial component lipopolysaccharide (LPS)5. We quantified the time-resolved release of 775 proteins, including 52 annotated cytokines, from only 150.000 primary cells per condition. The dynamic range of the secretory induction was at least 10,000 fold and we achieved sensitivity in the low picogram range. Comparison to the transcriptome revealed high correlation for some protein classes but also anti-correlation resulting from the transcriptionally decoupled release of lysosomal proteins. Using gene knockout (KO) mouse strains as genetic models with intracellular signaling adaptor deficiencies, we defined distinct secretory profiles depending on which arms of the signaling pathways are missing. We show that MyD88 dominates over TRIF in the number and fold-induction of secreted proteins6,7. Interestingly, the sum of the two signaling arms does not equal the wild-type response; instead, protein secretion is tuned by synergistic and predominantly redundant mechanisms. The kinetic data reveals that the release of anti-inflammatory proteins dampens the initial pro-inflammatory response. Our study provides a paradigm for the sensitive and time-resolved identification of receptor activation induced cellular secretomes, including proteins with unexpected extracellular presence, and allows the characterization of the underlying signal transduction pathways.
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