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accession-icon GSE22585
Genome-wide profiling of diel and circadian gene expression of the malaria vectorAnopheles gambiae
  • organism-icon Anopheles gambiae
  • sample-icon 104 Downloadable Samples
  • Technology Badge Icon Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)

Description

Anopheles gambiae,the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis ofA. gambiaehead and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.

Publication Title

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE85409
Transcriptional effects of Pentraxin-2 in fibrotic disease of the kidney
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 21 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

Pentraxin-2 (PTX-2) is a constitutive, anti-inflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Recent studies indicate that systemic delivery of recombinant PTX-2 inhibits inflammatory diseases associated with fibrosis by blocking pro-fibrotic macrophage activation and promoting anti-inflammatory and regulatory macrophages. Here we show that recombinant human PTX-2 (rhPTX-2) retards the progression of chronic kidney disease in Col4a3 mutant mice that develop Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously-delivered rhPTX-2 is detected in macrophages but is also found in tubular epithelial cells where it counteracts macrophage activation and is cytoprotective for the epithelium. We performed transcriptional profiling of whole kidney homogenates and human proximal tubule epithelial cells (PTECs) to identify pathways differentially activated or suppressed in response to treatment with PTX-2. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun and its binding partners, which form AP-1 complexes, as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun activation and reduces expression of AP-1 dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting.

Publication Title

Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE50439
Examining efficiency of enrichment of kidney pericyte-specific messages by TRAP (Translating Ribosome Affinity Purification)
  • organism-icon Mus musculus
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The long term goal is to define the transcriptional changes that accompany pericyte-to-myofibroblast transition in fibrotic kidney disease. Medullary pericytes are identified by their expression of a eGFPL10a fusion protein whose expression is driven by a Col1a1 promoter. Pericyte-specific RNA is generated by eGFP-affinity purification of polysomes from medullary lysates and then subject to microarray analysis.

Publication Title

Translational profiles of medullary myofibroblasts during kidney fibrosis.

Sample Metadata Fields

Sex, Specimen part, Time

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accession-icon GSE7586
Genome wide analysis of placental malaria
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Chronic inflammation during placental malaria (PM) caused by Plasmodium falciparum is most frequent in first-time mothers and is associated with poor maternal and fetal outcomes. In the first genome wide analysis of the local human response to sequestered malaria parasites, we identified genes associated with chronic PM, then localized the corresponding proteins and immune cell subsets in placental cryosections.

Publication Title

Genome-wide expression analysis of placental malaria reveals features of lymphoid neogenesis during chronic infection.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP045983
Tracking distinct RNA populations using efficient and reversible covalent chemistry
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500

Description

We describe a chemical method to label and purify 4-thiouridine (s4U) -containing RNA. We demonstrate that methanethiolsulfonate (MTS) reagents form disulfide bonds with s4U more efficiently than the commonly used HPDP-biotin, leading to higher yields and less biased enrichment. This increase in efficiency allowed us to use s4U-labeling to study global microRNA (miRNA) turnover in proliferating cultured human cells without perturbing global miRNA levels or the miRNA processing machinery. This improved chemistry will enhance methods that depend on tracking different populations of RNA such as 4-thiouridine-tagging to study tissue-specific transcription and dynamic transcriptome analysis (DTA) to study RNA turnover. Overall design: s4U metabolic labeling of RNA in 293T cells, followed by biochemical enrichment of labeled RNA with two biotinylation reagents, RNAs >200nt and miRNAs in separate experiments

Publication Title

Tracking Distinct RNA Populations Using Efficient and Reversible Covalent Chemistry.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE65848
Reconstructing human kidney microvasculature for the study of kidney injury
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Kidney peritubular capillaries are particularly susceptible to rarefaction and regeneration-limited after exposure to toxins or injuries. Studying these kidney microvessels remain challenging, primarily resulting from difficulties imaging in vivo, as well as isolating and culturing kidney microvascular cells in vitro, in particular in a three-dimensional (3D) microenvironment with proper hemodynamics. Here, we developed methods to isolate, purify, and characterize human kidney peritubular microvascular endothelial cells (hKMECs), and reconstituted a 3D kidney microvasculature in collagen matrix. Compared to other endothelial cells, isolated hKMECs are very sensitive to VEGF for survival and growth, and have a high vasculogenic but low angiogenic potential. Under flow, they formed a fenestrated endothelium with a comprehensive permeability barrier. When exposed to calcineurin inhibitors, hKMECs formed microvessels displayed cell retraction, broken fenestrae, and swollen endothelium, which led to a thrombogenic luminal wall and erythrocytes extravasations into the subendothelial space. Our study recapitulated the human kidney microvascular structure and function, and shed lights on potential mechanistic studies of kidney specific injuries and diseases.

Publication Title

A Novel Three-Dimensional Human Peritubular Microvascular System.

Sample Metadata Fields

Specimen part

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accession-icon SRP151504
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney
  • organism-icon Mus musculus
  • sample-icon 21 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;

Publication Title

Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.

Sample Metadata Fields

Sex, Age, Specimen part, Cell line, Subject

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accession-icon GSE12247
Mouse Mammary Gland Development
  • organism-icon Mus musculus
  • sample-icon 54 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

The mammary gland develops mainly postnatally, when during pregnancy the epithelium grows out into the mammary fat pad and forms a network of epithelial ducts. During pregnancy, these ducts branch and bud to form alveoli. These alveoli produce the milk during lactation. After 7 days of lactation, involution was induced by force weaning the pups. The newly formed epithelium undergoes apoptosis and is removed from the tissue by neighbouring epithelial cells. Tissue remodelling leads to a morphology resembling a gland of a pre-pregnant mouse. Microarray analysis was used to measure mRNA expression of genes during puberty, pregnancy, lactation and involution in a Balb/c mouse strain.

Publication Title

Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP096716
Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Inhibition of FOXO1 activity in kidney microvascular endothelial cells improves angiogenesis Overall design: Kidney microvascular endothelial cells were serum starved and treated with DMSO control or FOXO1 inhibitor for one hour, then stimulated with VEGF for 30 minutes

Publication Title

Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.

Sample Metadata Fields

Specimen part, Treatment, Subject, Time

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accession-icon SRP125683
Gene expression profile of human placenta from T. Cruzi infected mothers
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Overall design: Serodiagnosis of pregnant women was done by means of conventional serological methods and carried out by the respective health centres based on routine assays. In maternal and umbilical cord blood samples T. cruzi presence was tested using multiplex Real Time PCR as previously described [6]. Maternal infection with other pathogens that produce congenital transmission and adverse pregnancy outcome were considered as exclusion criteria, as well as missing data or incorrect sampling. Fresh normal placentas were obtained after labour from vaginal or caesarean deliveries and placed within 24 hours at 4°C. Each placenta was dissected and the middle section [7] at 2 cm distance from the umbilical cord was isolated and placed into RNAlater solution (Applied Biosystems, Foster City, CA). Total RNA was extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and stored at -80°C until used. Transcriptomic studies. A RNA-Seq experiment was done in 9 pools of 2 different placental RNA samples each: 3 pools (C1, C2 and C3) belonging to placentas from seronegative mothers (SN) and 6 pools (TC4 to TC9) from seropositive mothers (SP). Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. The cDNA Libraries were prepared according to Illumina''s TruSeq Stranded Total RNA with Ribo-Zero Gold for Human and a Hiseq 2.500 Illumina platform with 100 bp paired-end reads was used for sequencing

Publication Title

Alterations in Placental Gene Expression of Pregnant Women with Chronic Chagas Disease.

Sample Metadata Fields

Subject

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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