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.
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.
Specimen part
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The microRNA machinery regulates fasting-induced changes in gene expression and longevity in <i>Caenorhabditis elegans</i>.
No sample metadata fields
View SamplesIntermittent fasting (IF), a dietary restriction regimen, extends the lifespans of C. elegans and mammals by inducing gene expression changes. How fasting induces gene expression changes and longevity remains unclear. MicroRNAs (miRNAs) are small non-coding RNAs (approximately 22 nucleotides) that repress gene expression, and the expression of several miRNAs has been reported to be altered by fasting. In this study, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans. Our miRNA array analyses revealed that the expression levels of numerous miRNAs changed in adult worms after 48 hours of fasting. In addition to these changes, miRNA-mediated silencing complex (miRISC) components, including Argonaute proteins and GW182 proteins, and the miRNA-processing enzyme Drosha/DRSH-1, were up-regulated by fasting. Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knockout or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector. Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1, a gene encoding GW182, respectively. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme Drosha, play an important role in mediating IF-induced longevity via the regulation of fasting-induced gene expression changes.
The microRNA machinery regulates fasting-induced changes in gene expression and longevity in <i>Caenorhabditis elegans</i>.
No sample metadata fields
View SamplesThe gain of Protocadherin LKC (PCDH24) expression in colon carcinoma cell line HCT116 has been shown to induce contact inhibition, thereby completely abolishing tumor formation in vivo. To clarify the molecular mechanism, we performed DNA microarray analysis and compared gene-expression pattern between control and PCDH24-expressing HCT116 cells. Approximately 2000 genes were apparently changed their expression. Further proteomics analysis using 2-DE/MS confirmed the dramatic changes and provided additional information. We were aware that these changes are quite similar to the changes observed in epithelial-mesenchymal transition (EMT), most drastic changes in development and cancer metastasis. We thus further analyzed these changes using specific antibodies, and found distinct difference between these two phenomena. Among the differences, nuclear translocation of catenin beta 1 (CTNNB1) was inhibited by PCDH24-expression, subsequently some of the downstream nodes were suppressed. Although contact inhibition and cancer metastasis are completely opposite aspect of the cells, we expect that the identified differences will be key nodes to understand the relationship. We also expect that the nodes will be a target to modulate tumors arising stem cell transplantation (SCT), as well as a therapeutic target for cancer metastasis.
PCDH24-induced contact inhibition involves downregulation of beta-catenin signaling.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Sex, Age, Specimen part
View Samples(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans.
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Sex, Age, Specimen part
View SamplesThoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress.
Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation.
Specimen part, Treatment
View SamplesRNA-Sequencing of the trigeminal nucleus caudalis and spinal cord, dorsal horn in male naive rats (Wistar Han) of 10 weeks old Overall design: 6 naive rats were killed after 2 weeks of arrival, both trigeminal nucleus caudalis and spinal cord dorsal horn were dissected using laser capture microdissection of each rat.
Transcriptomic profiling of trigeminal nucleus caudalis and spinal cord dorsal horn.
No sample metadata fields
View SamplesThe aim of this study was to examine the role of indigenous lactobacilli in the physiological development of the stomach in mice using microarray analysis. In lactobacilli-associated gnotobiotic mice, an increased expression of the genes related to the muscle system development, such as nebulin and troponin, was observed. On the other hand, the expression of the gastrin gene dramatically decreased. A microarray analysis of the stomachs infected with H. pylori also showed both the up-regulation of muscle cell genes and the down-regulation of gastrin genes.
Role of indigenous lactobacilli in gastrin-mediated acid production in the mouse stomach.
No sample metadata fields
View SamplesWe sequenced mRNA from subcuteneous adipose tissue of 36 pigs (12 Low, 12 Mean and 12 High) to investigate expression profiling of obesity (porcine model) Overall design: Examination of mRNA levels in different obese states in a porcine model for human obesity
An integrative systems genetics approach reveals potential causal genes and pathways related to obesity.
Sex, Specimen part, Subject
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