Project description:This dataset comprises bulk RNA-seq and scRNA-seq data derived from thymic tissues of stroke-induced murine models. The data investigate the therapeutic effects of bone marrow-derived mesenchymal stem cell (BM-MSC)-originated migrasomes on stroke-induced thymic atrophy and immunosuppression. The results highlight the mechanistic role of BM-MSC migrasomes in reversing thymic involution and the immunosuppressive state through the specific delivery of the Peptidylprolyl Cis/Trans Isomerase (Pin1) to thymic epithelial cells (TECs). This dataset serves as a valuable resource for understanding post-stroke immunosuppression and the molecular basis of BM-MSC/migrasome-mediated therapy.
Project description:Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is not known. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as hESC by transcriptomics (RNA-Seq) and quantitative proteomics (nano LC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. A particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.
Project description:Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is not known. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as hESC by transcriptomics (RNA-Seq) and quantitative proteomics (nano LC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. A particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.
Project description:The connective tissue diseases (CTDs) are group of inflammatory disorders with overlapping clinical and serological manifestations. We have undertaken Lupus Extended Phenotype (LEAP) study in of a cohort of adult patients with CTDs, namely systemic lupus erythematosus, Sjogren's syndrome, mixed and undifferentiated CTD, limited and diffuse cutaneous systemic sclerosis and dermatomyositis. RNAseq was undertaken in 12 participants from 4 ‘cohorts’ based on interferon stimulated gene and autoantibodies analyses: 3 ISG positive and anti-Smith positive participants; 3 ISG positive and anti-Smith negative participants; 3 ISG negative and anti-Smith positive participants and 3 ISG negative and anti-Smith negative participants.
Project description:Expression data from hiPS lines after commitment towards mesenchymal lineage (hiPS-MSC) and expression data of mesenchymal lines (MSC), used as positive control of commitment. Following this, hiPS-MSC and MSC are seeded on scaffold to differentiate in a ligamentous (middle) and osseous (edges) part (post 21 days 3D differentiation) We used microarrays to validate efficient commitment of hiPS to generate hiPS-MSC and do whole transcriptome comparison of hiPS-MSC vs isolated MSC (positive control) and then compare the enhanced biological functions after differentiation of these cells on a scaffold
Project description:Mesenchymal stromal cells (MSC) are promising stem cell therapy for treating cardiovascular and other degenerative diseases. Diabetes affects the functional capability of MSC and impedes cell-based therapy. Despite numerous studies, the impact of diabetes on MSC myocardial reparative activity, metabolic fingerprint, and the mechanism of dysfunction remains inadequately understood. We demonstrated that the transplantation of diabetic-MSC (db/db-MSC) into the ischemic myocardium of mice does not confer cardiac benefit post-MI. Metabolomic studies identified defective energy metabolism in db/db-MSC. Furthermore, we found that glypican-3 (GPC3), a heparan sulfate proteoglycan, is highly upregulated in db/db-MSC and is involved in metabolic alterations in db/db-MSC via pyruvate kinase M2 activation. GPC3-knockdown reprogrammed-db/db-MSC restored their energy metabolic rates, immunomodulation, angiogenesis, and cardiac reparative activities. Together, these data indicate that GPC3-metabolic reprogramming in diabetic MSC may represent a strategy to enhance MSC-based therapeutics for myocardial repair in diabetic patients.
Project description:Mesenchymal stromal cells (MSC) are ideal candidates for cell therapies, due to their immune-regulatory and regenerative properties. We have previously reported that lung-derived MSC are tissue-resident cells with lung-specific properties compared to bone marrow-derived MSC. Assessing relevant molecular differences between lung-MSC and bone marrow-MSC is important, given that such differences may impact their behavior and potential therapeutic use. Here, we present an in-depth mass spectrometry (MS) based strategy to investigate the proteomes of lung-MSC and bone marrow-MSC. The MS-strategy relies on label free quantitative data-independent acquisition (DIA) analysis and targeted data analysis using a MSC specific spectral library. We identified several significantly differentially expressed proteins between lung-MSC and bone marrow-MSC within the cell layer (352 proteins) and in the conditioned medium (49 proteins). Bioinformatics analysis revealed differences in regulation of cell proliferation, which was functionally confirmed by decreasing proliferation rate through Cytochrome P450 stimulation. Our study reveals important tissue-specific differences within proteome and matrisome profiles between lung- and bone marrow-derived MSC that may influence their behavior and affect the clinical outcome when used for cell-therapy.
Project description:Leukemia cells instruct their surrounding bone marrow microenvironment (BMM) rendering it hospitable to leukemia cell survival. Conversely, how cells of the BMM influence leukemia progression is less well understood. Pleckstrin homology domain family M member 1 (PLEKHM1) serves as a hub between fusion and secretion of intracellular vesicles. Here, we performed label-free quantitative proteomics to investigate the exosomal cargo released by BMM-derived mesenchymal stromal cells (MSC) lacking Plekhm1 compared to wild-type cells.