Gene expression analysis in hLECs treated with gain of function or loss of function of MDK in human melanoma cells. Overall design: Biological triplicates of hLEC treated for 3 days with EGM-2 MV conditioned media of melanoma cells. Cell line SK-Mel-147 KD for MDK (shMDK) and its corresponding control (shCtrl (LoF) and WM164 cell line overexpressing MDK (MDK) or an empty vector (NEG) (GoF) were used to produce the conditioned media.
Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.
Specimen part, Subject
View SamplesThe goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.
Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia. Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality. Overall design: High temporal analysis of global gene expression in the DRG following spared nerve injury (SNI) correlated with behavior taken at the same time points. Expression and behavioral sensitivity taken at least daily over the first 10 days post SNI.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Cell line, Subject
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia (DRG). Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related, whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas, depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesThe anticarcinogenic activity of hydroxytyrosyl ethyl ether (HTy-Et) compared to its precursor hydroxytyrosol (HTy) has been studied in human Caco-2 colon adenocarcinoma cells.
Hydroxytyrosyl ethyl ether exhibits stronger intestinal anticarcinogenic potency and effects on transcript profiles compared to hydroxytyrosol.
Specimen part, Disease, Disease stage, Cell line
View SamplesIKKbeta is a subunit of the IkB kinase (IKK) complex required for NF-kB activation in response to pro-inflammatory signals. NF-kB regulates the expression of many genes involved in inflammation, immunity and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. We here report the alterations caused by increased IKKbeta activity in basal cells of the skin of transgenic mice.
IKKbeta leads to an inflammatory skin disease resembling interface dermatitis.
Sex, Age, Specimen part
View SamplesThe goal of this study is to simultaneously interrogate the gene expression programs in human host cells (human foreskin fibroblasts) infected with the intracellular parasite Trypanosoma cruzi. We conducted high-resolution sequencing of the transcriptomes of T. cruzi and infected human foreskin fibroblasts (HFFs) using an RNA-seq approach. An array of computational tools was applied to map reads to the T. cruzi and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for T. cruzi genes at at various time points post-infection enabling us to identify co-expression patterns that correlate with the biology of the parasite. We also conducted a time course of infection in host cells to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. These data provide the first glimpse of T. cruzi gene expression programs that are uniquely activated in the context of intracellular infection along with the transcriptional response of the human host cell. The study provides a solid framework for future functional and genomic studies of Chagas disease as well as intracellular pathogenesis in general.
Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.
No sample metadata fields
View SamplesAberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1
Constitutively active Akt induces ectodermal defects and impaired bone morphogenetic protein signaling.
Age, Specimen part
View SamplesMouse and human stem cells with features similar to those of embryonic stem cells have been derived from testicular cells. Although pluripotent stem cells have been obtained from defined germline stem cells (GSCs) of mouse neonatal testis, only multipotent stem cells have been obtained so far from defined cells of mouse adult testis. In this study we describe a robust and reproducible protocol for obtaining germline-derived pluripotent stem (gPS) cells from adult unipotent GSCs. Pluripotency of gPS cells was confirmed by in vitro and in vivo differentiation, including germ cell contribution and transmission. As determined by clonal analyses, gPS cells indeed originate from unipotent GSCs. We propose that the conversion process requires a GSC culture microenvironment that depends on the initial number of plated GSCs and the length of culture time.
Induction of pluripotency in adult unipotent germline stem cells.
No sample metadata fields
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