Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood.
A role for RNA post-transcriptional regulation in satellite cell activation.
Sex, Specimen part
View SamplesHeterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice. Overall design: RNAseq data of T47D cells expressing HA-tagged wild-type GATA3 (HA_GATA3_wt) or one of two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2).
GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice.
Specimen part, Cell line, Subject
View SamplesDuring neonatal development, skeletal muscle grows dramatically by myonuclei accretion to existing fibers and hypertophic growth of fibers with protein synthesis.
An NF-κB--EphrinA5-Dependent Communication between NG2(+) Interstitial Cells and Myoblasts Promotes Muscle Growth in Neonates.
Specimen part
View SamplesDuring neonatal development, skeletal muscle grows dramatically by myonuclei accretion to existing fibers and hypertophic growth of fibers with protein synthesis. Overall design: To understand molecular mechanism underlying neonatal muscle growth, we used RNAseq to profile the global program of gene expressions especially involved in myoblast fusion, migration, and muscle fiber growth by itself. We used two biological replicates for each time point.
An NF-κB--EphrinA5-Dependent Communication between NG2(+) Interstitial Cells and Myoblasts Promotes Muscle Growth in Neonates.
Specimen part, Subject
View SamplesAnticipating the risk for infectious disease during space exploration and habitation is a critical factor to ensure safety, health and performance of the crewmembers. As a ubiquitous environmental organism that is occasionally part of the human flora, Pseudomonas aeruginosa could pose a health hazard for the immuno-compromised astronauts. In order to gain insights in the behavior of P. aeruginosa in spaceflight conditions, two spaceflight-analogue culture systems, i.e. the rotating wall vessel (RWV) and the random position machine (RPM), were used. Microarray analysis of P. aeruginosa PAO1 grown in the low shear modeled microgravity (LSMMG) environment of the RWV compared to the normal gravity control (NG), revealed a regulatory role for AlgU (RpoE). Specifically, P. aeruginosa cultured in LSMMG exhibited increased alginate production and up-regulation of AlgU-controlled transcripts, including those encoding stress-related proteins. This study also shows the involvement of Hfq in the LSMMG response, consistent with its previously identified role in the Salmonella LSMMG- and spaceflight response. Furthermore, cultivation in LSMMG increased heat- and oxidative stress resistance and caused a decrease in the culture oxygen transfer rate. Interestingly, the global transcriptional response of P. aeruginosa grown in the RPM was similar to that in NG. The possible role of differences in fluid mixing between the RWV and RPM is discussed, with the overall collective data favoring the RWV as the optimal model to study the LSMMG-response of suspended cells. This study represents a first step towards the identification of specific virulence mechanisms of P. aeruginosa activated in response to spaceflight-analogue conditions, and could direct future research regarding the risk assessment and prevention of Pseudomonas infections for the crew in flight and the general public.
Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation.
No sample metadata fields
View SamplesAtopic dermatitis, a chronic inflammatory skin disease with increasing prevalance, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31-dependent gene expression was determined in 3-dimensional organotypic skin models.
Control of the Physical and Antimicrobial Skin Barrier by an IL-31-IL-1 Signaling Network.
Sex, Specimen part
View SamplesThe similarity in gene-expression profiles suggest that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these three subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of a paraganglioma regardless of the genetic background.
Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis.
No sample metadata fields
View SamplesPolycomb-mediated gene repression plays an important role in adult stem cell maintenance. We knocked out (using the inducible AhCre-LoxP system) Polycomb genes Eed and Ezh2 in the intestine for 6 weeks, after which crypts - the small intestinal stem cell zone - were harvested and RNA sequenced. We found Wnt, Notch and cell cycle pathways to be affected in Eed knockout (KO) but not Ezh2 KO crypts. Direct targets of Eed were determined by comparing this data with ChIP-sequencing. Overall design: Small intestinal crypt mRNA profiles of 6 weeks-induced 12 weeks old Eed KO, Ezh2 KO and WT mice (all triplicates) as well as 10 days-induced Eed KO and WT organoids (duplicates) were generated by RNA sequencing over two runs and using IlluminaHiseq2000 and Hiseq2500.
Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells.
Specimen part, Subject
View SamplesMore than 7% of the Pseudomonas aeruginosa genes are encoding transcriptional regulators, many of which with unknown functions. Among them, those belonging to the LysR family are the most represented. The PA4203 gene lies upstream of the previously characterized ppgL gene (PA4204), which encodes a periplasmic gluconolactonase, which detoxifies gluconolactone by converting it to gluconate. Upstream of PA4203 and in the opposite orientation are the PA4202 gene coding for a nitronate monooxygenase and ddlA (PA4201) encoding a D-alanine alanine ligase. This genetic organization is conserved in all P. aeruginosa genomes, but not in other pseudomonads. The intergenic regions between PA4203 and ppgL, and PA4202 are very short (79 and 107 nucleotides, respectively). PA4203 is a repressor of PA4202 and of its own transcription. A chromatin immunoprecipation analysis confirmed the presence of a single PA4203 binding site between PA4202 and PA4203. Electrophoretic mobility shift assays (EMSAs) with the purified PA4203 protein and in41 gel footprinting with the 1, 10-phenanthroline-copper ion, combined with primer extension analysis to determine transcriptional startpoints allowed the identification of a LysR binding motive in the PA4202 and PA4203 intergenic region. Despite this, a transcriptome analysis revealed more genes to be affected in a PA4203 mutant, likely due to the overexpression of the nitronate monooxygenase (PA4202). Deletion of the PA4202 gene resulted in an increased sensitivity of the cells to 3- nitropropionic acid (3-NPA).
Pseudomonas aeruginosa LysR PA4203 regulator NmoR acts as a repressor of the PA4202 nmoA gene, encoding a nitronate monooxygenase.
No sample metadata fields
View SamplesA genetic association between the ANP32A gene and osteoarthritis has been suggested. We compared transcriptome profiles of the articular cartilage and subchondral bone from mice deficient in ANP32A with wild-type mice to get insights into the role of ANP32A in the pathogenesis of ostearthritis.
ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone.
Age, Specimen part
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