Gene expression signatures for IhhN protein induced cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74021 | GEO | 2015/10/15
SECONDARY ACCESSION(S): PRJNA298758
REPOSITORIES: GEO
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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 miRNA expression profiling as a discovery platform to identify miRNAs with the potential to take part in Gli1-mediated cis-regulatory network.
2015-10-15 | GSE74020 | GEO
Project description:Indian Hedgehog signaling (IHH) regulates multiple aspects of endochondral bone formation and ultimately regulates expression of downstream genes by Gli zinc finger domain-containing transcription regulators in the cartilage development. In response to a BDA1 mutant IHH induction, Gli1-mediated downstream regulatory pattern might be quite different from that in response to wild type IHH induction.
2015-10-15 | GSE74022 | GEO
Project description:In order to characterize mRNA expression in the growth plate, we microdissected postnatal rat growth plates into their constituent zones and used microarray analysis to assess the abundences of individual transcripts. Expression patterns of PTHrP and Ihh-related genes were confirmed using real-time PCR. Using a gli1-lacZ mouse, Gli1 expression, presumably representing Ihh signaling, was visualized during pre- and postnatal development.
2010-12-01 | GSE23432 | GEO
Project description:In order to characterize mRNA expression in the growth plate, we microdissected postnatal rat growth plates into their constituent zones and used microarray analysis to assess the abundences of individual transcripts. Expression patterns of PTHrP and Ihh-related genes were confirmed using real-time PCR. Using a gli1-lacZ mouse, Gli1 expression, presumably representing Ihh signaling, was visualized during pre- and postnatal development. Microdissection was used to collect individual growth plate zones from proximal tibiae of 1-wk rats and gene expression was analyzed using microarray.
2010-12-01 | E-GEOD-23432 | biostudies-arrayexpress
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.
2023-12-05 | GSE183253 | GEO
Project description:CCD, which is characterized by hypoplastic clavicles, open fontanelles, supernumerary teeth, and short stature, are caused by heterozygous mutation of RUNX2. However, the reason why the suture closure is severely impaired in CCD patients remains to be clarified. The closure of posterior frontal (PF) and sagittal sutures was completely interrupted in Runx2+/– mice, and the proliferation of the suture mesenchymal cells was reduced compared with that in wild-type mice. To reveal the molecular mechanism, the differentially expressed genes between wild-type and Runx2+/– PF sutures were identified by microarray and real-time RT-PCR analyses. The expression of hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, including Gli1, Ptch1, Ihh, Fgfr1-3, Tcf7, Wnt10b, Wnt1, and Pth1r, was reduced in PF sutures of Runx2+/– mice. These findings indicated that more than half dosage of Runx2 is required for the proliferation of suture mesenchymal cells, their commitment into osteoblast-lineage cells, and the induction of the hedgehog, Fgf, Wnt, and Pthlh signaling pathway gene expression in the sutures.
2019-10-09 | GSE119523 | GEO
Project description:Prostate embryonic development, pubertal and adult growth, maintenance, and regeneration are regulated through androgen signaling-mediated mesenchymal epithelial interactions. Specifically, the essential role of mesenchymal androgen signaling in the development of prostate epithelium has been observed for over 30 years. However, the identity of the mesenchymal cells responsible for this paracrine regulation and related mechanisms are still unknown. Here, we provide the first demonstration of an indispensable role of the androgen receptor (AR) in sonic hedgehog (SHH) responsive Gli1-expressing cells, in regulating prostate development, growth, and regeneration. Selective deletion of AR expression in Gli1-expressing cells during embryogenesis disrupts prostatic budding and impairs prostate development and formation. Tissue recombination assays showed that urogenital mesenchyme (UGM) containing AR-deficient mesenchymal Gli1-expressing cells combined with wildtype urogenital epithelium (UGE) failed to develop normal prostate tissue in the presence of androgens, revealing the decisive role of AR in mesenchymal SHH responsive cells in prostate development. Prepubescent deletion of AR expression in Gli1 expressing cells resulted in severe impairment of androgen-induced prostate growth and regeneration. RNA-sequencing analysis showed significant alterations in signaling pathways related to prostate development, stem cells, organ morphogenesis appeared showed significant changes in AR-deficient Gli1-expressing cells. The transforming growth factor β (TGFβ) pathway was up-regulated in AR-deficient Gli1-expressing cells. We further demonstrated the activation of TGF- b signaling in AR deleted prostatic Gli1-expressing cells, which inhibits prostate epithelium growth through paracrine regulation. These data demonstrate a novel role of the AR in the Gli1-expressing cellular niche for regulating prostatic cell fate, morphogenesis, and renewal, and elucidate the mechanism by which mesenchymal androgen-signaling through SHH-responsive cells elicits the growth and regeneration of prostate epithelium.
2020-01-03 | GSE140823 | GEO
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
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 We conditionally ablated Indian hedgehog in the mouse uterus using the PRcre mouse model (PRcre/+Ihhf/f; Ihhd/d). High density DNA microarray analysis was performed on Day -1 of the artificial decidual response on Ihhf/f and Ihhd/d uteri.
2010-03-06 | E-GEOD-19517 | biostudies-arrayexpress
Project description:We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter, and this gene pair synergistically promoted the development of non-small-cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remain obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from the TCGA database by the correlation analysis of gene expression and gene set enrichment analysis (GSEA), revealing that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected by RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2 and BUB1, involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with shorter overall survival of LSCC patients. Taken together, our results indicated that GLI1/2 mediated the expression of the PRR11-SKA2-centric gene set which served as unfavorable prognostic indicators for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC.
2022-11-10 | GSE161226 | GEO