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GSE60099
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The platelet-derived growth factor receptor alpha (PDGFR) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFR pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFR in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFR signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFR with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.
Publication Title
Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The platelet-derived growth factor receptor alpha (PDGFR) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFR pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFR in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFR signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFR with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.
Publication Title
Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina HiSeq 2500
Description
The liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase C?-mediated NF-?B activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca2+ levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver stage development of the P. berghei rodent malaria parasite and the human P. falciparum parasite also. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis. Overall design: To explore the molecular mechanisms by which the HGF/MET/PKC?/NF-?B pathway regulates P. berghei sporozoite development in hepatocytes, we compared the gene expression patterns in wild-type and PKC?-KO Huh7 cells treated or not treated with HGF. We also analyzed the gene expression profiles in wild type and PKC?-KO Huh7 cells uninfected or infected with P. berghei sporozoites.
Publication Title
CXCR4 regulates <i>Plasmodium</i> development in mouse and human hepatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lactic acid bacteria confer a variety of health benefits. Here we investigate the mechanisms by which Lactobacillus brevis KB290 enhances cell-mediated cytotoxic activity. We fed a diet containing KB290 (3 10^9 colony-forming units/g) , or potato starch, to 9-week-old female BALB/c mice for 1, 4, 7, or 14 days and examined the cytotoxic activity of splenocytes was measured. RNA was extracted from the spleen and analyzed for gene expression by DNA microarray.
Publication Title
Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Publication Title
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
iPSC-derived NSPCs, which were induced by two different protocols (Embryoid body or Neural rosette) followed by expansion in free-floating culture (neurospheres), had closely resembled profiles.
Publication Title
Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.
Sample Metadata Fields
Sex, Race
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The entire small intestine was obseved by balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.
Publication Title
Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
We have previously established an in vitro tissue culture system (named VISUAL; Kondo et al., 2016), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
Publication Title
BES1 and BZR1 Redundantly Promote Phloem and Xylem Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Arabidopsis thaliana
- 17 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Xylem consists of three types of cells: vessel cells, also referred to as tracheary elements (TEs), parenchyma cells, and fiber cells. TE differentiation includes two essential processes, programmed cell death (PCD) and secondary cell wall formation. These two processes are tightly coupled. However, little is known about the molecular mechanism of their gene regulation. Here, we show that VASCULAR-RELATED NAC-DOMAIN 6 (VND6), a master regulator of TEs, regulates these processes in a coordinated manner. We first identified specific genes downstream of VND6 by comparing them with those of SECONDARY WALL-ASSOCIATES NAC DOMAIN PROTEIN1 (SND1), a master regulator of xylem fiber cells, with transformed suspension culture cells in microarray experiments.
Publication Title
Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 directly regulates the genes that govern programmed cell death and secondary wall formation during xylem differentiation.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
MED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-dependent target genes; however, the genes in this subset varies between cell types. MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown. We generated Med23 conditional knockout mice and induced Med23 deletion in early T cell development using the lineage specific Lck-Cre transgene. While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T cell master regulatory transcription factor. Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects. Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression. In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2.
Publication Title
T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs.
Sample Metadata Fields
Sex, Specimen part
View Samples