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GSE69991
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A widely shared view reads that 'MSCs' are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with the ubiquitous 'pericytes.' Using stringent in vivo differentiation assays and transcriptome analysis, we show here that human cell populations from different anatomical sources, which would all be regarded as 'MSCs' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis further reveals that muscle 'pericytes,' which are not spontaneously osteo-chondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called 'MSCs,' with important applicative implications. The data also support the view that rather than a uniform class of 'MSCs,' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, likely of different developmental origin.
Publication Title
No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mesoangioblasts are stem/progenitor cells derived from a subset of pericytes expressing alkaline phosphatase. They have been shown to ameliorate muscular dystrophies (currently incurable diseases) in different animal models and are now undergoing clinical experimentation for Duchenne muscular dystrophy. We show here that patients affected by limb-girdle muscular dystrophy 2D (LGMD2D, characterized by -sarcoglycan deficit) have a reduction of this subset of pericytes and hence mesoangioblast could not be derived for cell therapy. Therefore, we reprogrammed LGMD2D fibroblasts and myoblasts to induced pluripotent stem cells (iPSCs) and developed a protocol for the derivation of mesoangioblast-like cells from them. These cells can be expanded and genetically corrected with a muscle-specific lentiviral vector expressing human -sarcoglycan. Upon transplantation into ad hoc generated -sarcoglycan-null immunodeficient mice, they generate myofibers expressing -sarcoglycan. This approach may be useful for muscular dystrophies that show a reduction of resident progenitors and provides evidence of pre-clinical safety and efficacy of disease-specific iPSCs.
Publication Title
Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regeneration of skeletal muscle is dependent on the function of tissue-resident muscle stem cells (MuSC), known as satellite cells. MuSC dysfunction is central to muscle pathophysiology, including in age-associated loss of muscle regenerative capacity and congenital disorders such as Duchenne muscular dystrophy. Despite the central role of satellite cells in muscle regeneration, the signals controlling the balance between muscle stem cell quiescence, proliferation, and differentiation remain incompletely understood. Knowledge of the signals that maintain a quiescent state is particularly lacking, yet such cues are crucial to maintaining a stem cell reservoir that can meet the needs of regeneration throughout life. Here we identify Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent and essential trans-acting regulator of satellite cell quiescence. Key to this discovery is the development of a novel in vivo imaging-based screening strategy allowing identification of proteins that do not induce in vitro proliferation, but instead maintain MuSCs in a non-mitotic state, poised for rapid robust expansion upon transplantation. We demonstrate that OSM induces reversible exit from the cell cycle and induction of a global transcriptional program significantly enriched within a newly established satellite cell quiescence signature. Genetic ablation of the OSM receptor in mice demonstrates that signaling via OSM/R is essential for maintenance of satellite cell quiescence, and for proper skeletal muscle regeneration in vivo. Given that aberrant activation and exhaustion of stem cells is seen in a variety of disorders, OSM constitutes an attractive therapeutic target in muscle disease states.
Publication Title
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell differentiation is known to involve changes in RNA expression, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of embryonic stem cells (ESCs) into embyroid bodies (EBs) by integrating conventional transcriptome analysis with global assessment of ribosome loading. Differentiation was accompanied by an anabolic switch, characterized by global increases in transcript abundance, polysome content, protein synthesis rates and protein content. Furthermore, 78% of expressed transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Elevated protein synthesis was accompanied by enhanced phosphorylation of eIF-4E binding protein, suggesting regulation by the mTOR pathway.
Publication Title
A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
Publication Title
Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We have discovered rifampicin as a glycation inhibitor, which increases life span in C elegans. In order to understand the mechanism of rifampicin action, microarray analysis was performed to study the changes in gene expression brought about by the drug.
Publication Title
Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This study identifies miR-198 as a potential inhibitor of keratinocyte migration in skin
Publication Title
'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The majority of sporadic colorectal cancer cases are initiated by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Several pre-clinical models carrying germline mutations in the endogenous mouse Apc tumor supressor gene have been generated and their phenotype characterized. The predisposition of these mouse models to multiple intestinal adenomas closely resembles the FAP phenotype at the molecular, cellular and phenotypic level and may prove valuable to elucidate the molecular and cellular mechanisms underlying colorectal tumorigenesis. The goal of this study is to establish an expression signature characteristic of intestinal tumors characterized by the inactivation of Apc.
Publication Title
Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.
Publication Title
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Sample Metadata Fields
Specimen part, Treatment
View Samples