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GSE65402
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined due to a lack of functional subclasses. Here we reveal the presence of multiple lineages of dermal fibroblasts within the dorsal back. Genetic lineage tracing and transplantation assays demonstrate that the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation is carried out by a single, somitic-derived fibroblast lineage. Reciprocal transplantation of distinct fibroblast lineages between the dorsal back and oral cavity induced ectopic dermal architectures that mimic their placeof-origin. These studies demonstrate that intra and inter-site diversity of dermal architectures are set embryonically and maintained postnatally by distinct lineages of fibroblasts. Lineage-specific cell ablation using transgenic-mediated expression of the simian diphtheria toxin receptor in conjunction with localized administration of diphtheria toxin led to diminished connective tissue deposition in wounds and significantly reduced melanoma growth in the dorsal skin of mice. Using flow cytometry and in silico approaches, we identify CD26/DPP4 as a surface marker that allows for the isolation of this fibrogenic, scar-forming lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. The identification and prospective isolation of these lineages holds promise for translational medicine aimed at in vivo modulation of their fibrogenic behavior.
Publication Title
Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Publication Title
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
Illumina Genome Analyzer II
Description
Backgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
Publication Title
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
MicroRNAs are a class of short ~22 nucleotide RNAs predicted to regulate nearly half of all protein-coding genes, including many involved in basal cellular processes and organismal development. Although both increases and decreases in the levels of specific miRNAs have been shown to promote tumor development, a global reduction in miRNAs is commonly observed in various human tumors. However, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer-null somatic cells can be isolated readily in vitro, maintain the characteristics of Dicer-expressing controls and remain stably proliferative. Furthermore, Dicer-null cells from a sarcoma cell line, though depleted of miRNAs, are competent for tumor formation. Hence, miRNA levels in cancer may be maintained in vivo by a complex stabilizing selection in the intratumoral environment. Overall design: Small RNAs from tumor cell lines (murine sarcoma KrasG12D, p53 -/-) with and without Dicer (Dicer f/-, Dicer -/-) were analyzed.
Publication Title
Proliferation and tumorigenesis of a murine sarcoma cell line in the absence of DICER1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Overall design: mRNAs from adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-), were analyzed. WT and KO cells were transfected with a nontargeting control siRNA. KO cells were separately transfected with a synthetic let-7g siRNA duplex, or an siRNA targeting Nr6a1.
Publication Title
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells. Overall design: Splenic follicular IgD low and IgD high , and MZ B cells were sorted by FACS from naïve 8-10 weeks old mice. Total RNA was isolated from the sorted cells using RNAqueous® -4PCR kit and RNA sequencing was performed. Splenocytes from five mice were pooled for each sorting. Three independent sorting was performed for each B cell subset.
Publication Title
Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function.
Publication Title
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Overall design: mRNAs from Flag-HA-NR6A1-overexpressing Dicer wild-type adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) and vector-only Dicer WT MSCs were analyzed.
Publication Title
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Overall design: Small RNAs from adult mesenchymal stem cells (immortalized clonal lines of murine MSCs) with and without Dicer (Dicer f/f, Dicer -/-) were analyzed.
Publication Title
Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
Sample Metadata Fields
Specimen part, Cell line
View Samples