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MiRNA gene expression signatures for IhhN protein induced cells

ABSTRACT: Previous studies demonstrated that hererozygous missense mutations in IHH could lead to a decreasing IHH signaling efficacy and cause brachydactyly type A1 (BDA1). For revealing difference of Gli1-mediated downstream regulatory effects between wild type IHH signaling and E95K mutant IHH signaling, we have employed whole genome microarray miRNA expression profiling as a discovery platform to identify miRNAs with the potential to take part in Gli1-mediated cis-regulatory network.

ORGANISM(S): Mus musculus

PROVIDER: GSE74020 | GEO | 2015/10/15

SECONDARY ACCESSION(S): PRJNA298757

REPOSITORIES: GEO

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Gene expression signatures for IhhN protein induced cells

Project description:Previous studies demonstrated that hererozygous missense mutations in IHH could lead to a decreasing IHH signaling efficacy and cause brachydactyly type A1 (BDA1). For revealing difference of Gli1-mediated downstream regulatory effects between wild type IHH signaling and E95K mutant IHH signaling, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to be targets of Gli1 cis-regulation.

2015-10-15 | GSE74021 | GEO

Chip-chip from C3H10T1/2 cells with Gli1

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Indian Hedgehog Signaling in the Postnatal Growth Plate

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Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1

Project description:Brachydactyly type A1 (BDA1), due to mutations in IHH, is characterized with shortened and/or missing middle phalangeal bones. These mutations alter the capacity and range of IHH signaling, reducing mesenchymal cells recruiting into the cartilage anlagen of a growing digit, result in a shorter middle phalange. However, reason for a missing middle phalange is unclear. Here, in IhhE95K BDA1 mouse, we showed a link to impaired apoptosis normally needed for interzone cavitation, thus a joint is not formed and the middle phalange is deemed absence. Hedgehog interacting partners (PTCH, CDON, GAS1and HHIP) are expressed in the interzone. Our data support a model for interzone cavitation, where CDON/GAS1 function as dependency receptors. Normally, IHH level is low at the center of the interzone, and the “ligand-free” CDON/GAS1 activate cell death for cavitation. In BDA1 joint, this is suppressed due to excess IHH. Our findings provided new insights into the role of IHH and CDON in joint formation, with relevance to hedgehog signaling in developmental biology.

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ChIP-seq analysis of Gli1 and Sox2 input to neural progenitor program and integration with actve histone marks

Project description:In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue appropriate regulatory programs. To elucidate Shh/Gli regulation of neural fate sepcification, we performed Gli1 ChIP-Seq analysis. We further analyzed two transcription factors whose motifs were enriched in Gli1 ChIP data (Sox2 and Foxa2). Two active histone marks (H3K4me2 and H3K27ac) were additionally analyzed to study activity status of Shh-responsive cis-elements. Active enhancer histone marks and transcription factor binding patterns were obtained from neuralized emrbyoid bodies. Biological replicates were performed for Gli1 and mock FLAG chips. Histone profiling for enhancer marks were taken from time course experiment performed in parallel.

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LncRNA Gm26917 promotes macrophage differentiation by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury

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ChIP-seq analysis of Gli1 and Sox2 input to neural progenitor program and integration with actve histone marks

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Gene expression profiling of conditional ablation of Indian hedgehog in the mouse uterus

Project description:Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling. Keywords: two group comparison

2010-03-01 | GSE19517 | GEO

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