This SuperSeries is composed of the SubSeries listed below.
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
View SamplesCombinatorial recruitment of CREB, C/EBPb and Jun determines activation of promoters upon keratinocyte differentiation
Combinatorial recruitment of CREB, C/EBPβ and c-Jun determines activation of promoters upon keratinocyte differentiation.
Specimen part, Treatment
View SamplesRetrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate ~900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and ~4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified ~400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response
Signaling to transcription networks in the neuronal retrograde injury response.
No sample metadata fields
View SamplesWe used microarray to detect pathway differences in the various brain regions in a monogenic in mucopolysaccharidosis type VII ( MPS VII ), a mouse model of a lysosomal storage disease
Dysregulation of gene expression in a lysosomal storage disease varies between brain regions implicating unexpected mechanisms of neuropathology.
Specimen part
View SamplesWe used microarray to detect pathway differences in the hippocampus in mucopolysaccharidosis type VII ( MPS VII ), a mouse model of a lysosomal storage disease
Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus.
Sex, Age, Specimen part
View SamplesThe adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging.
Lnk deficiency partially mitigates hematopoietic stem cell aging.
Specimen part
View SamplesPrevious studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions.
Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice.
Sex, Specimen part, Treatment
View SamplesPurpose: provide evidence that RNA-seq can add information to transcriptome profiling already discovered by other technologies for atopic dermatitis Methods: mRNA profiles of 20 atopic dermatitis were analyzed to compare lesional and non-lesional skin, then transcriptomes found by reads were compared to Microarray and RT-PCR Results:RNA-seq provided complementary genes to AD transcriptome IL-36 and TREM-1 Conclusions: Our study represents the first analysis of lesional AD tissue by RNA-seq and comparison to microarray and RT-PCR Overall design: paired biopsies from lesional and non-lesional tissue of 20 patients sequenced by RNA-seq
RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications.
No sample metadata fields
View SamplesAn improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1? TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8+ T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8+ T cell responses upon immunotherapy. Overall design: (i) RNAseq of Wild Type Naïve-like, Memory-like and Effector-like subpopulations of PD1-CD8+ Tumor infiltrating lymphocytes isolated from MC38-OVA. CD62LhiSlamf7-CX3CR1-, CD62L-Slamf7hiCX3CR1- and CD62L-Slamf7hiCX3CR1+ subsets within PD-1-CD8+ TILs (ii) RNAseq from WT mice, Tim-3+PD-1+ and Tim-3-PD-1- CD8+ TILs were isolated by cell sorting from MC38-OVA tumor-bearing mice that were treated with anti-PD-1 and anti-Tim-3 antibodies or isotype controls. (iii) Droplet-based single-cell RNA-Seq of Tim-3-PD-1- CD8+ TILs from MC38-OVA tumor-bearing WT mice that were treated with anti-PD-1 and anti-Tim-3 antibodies or isotype controls.
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1<sup>-</sup>CD8<sup>+</sup> Tumor-Infiltrating T Cells.
Specimen part, Cell line, Treatment, Subject
View SamplesThe adaptor protein MERIT40 is a core subunit of deubiquitinating (DUB) complexes that specifically cleave Lysine63-polyubiquitin chains. We found that MERIT40 is an important negative regulator of hematopoietic stem cell (HSC) homeostasis, quiescence and self-renewal. This study aims to investigate the molecular mechanism by which MERIT40 regulates HSC expansion and cell cycle. We performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from WT and Merit40-/- mice. Results identify select MERIT40-mediated pathways with potential involvement in HSC cell cycle regulation.
MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling.
Specimen part
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