Ontology highlight
ABSTRACT:
PROVIDER: PRJNA592618 | ENA |
REPOSITORIES: ENA
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Project description:The imaginal discs of Drosophila melanogaster, where most known Hedgehog (Hh) signaling target genes are expressed with a restricted pattern, offers an accessible model system for identifying novel targets of the Hh signaling pathway. In the wing discs, cells near the A/P compartment boundary (B: ptc+) receive the highest level of Hh stimulation, A cells (A: hh-) further from the border receive lower levels of stimulation, while P cells (P: hh+) do not respond to Hh. To identify target genes whose expression is controlled by Hh signaling activity, we performed a systematic comparison of gene expression profiles among the A cells (A: hh-), the A cells adjacent to the A/P compartment boundary (B: ptc+), and P cells (P: hh+) via microarray analysis.
2021-07-15 | GSE180120 | GEO
Project description:We report Hedgehog signaling responsive genes with or without Esrrb in NI3T3 cells. Using Hh-responsive cells, we used RNA-Seq to find Hh responsive genes. In addition, we tested Esrrb's modification on Hh target genes' response.
2015-11-06 | GSE71209 | GEO
Project description:We report Hedgehog signaling responsive genes with or without Esrrb in NI3T3 cells. Using Hh-responsive cells, we used RNA-Seq to find Hh responsive genes. In addition, we tested Esrrb's modification on Hh target genes' response. Control vector transfected cells with vehicle treatment, Esrrb expression vector transfected cell with vehicle treatment, control vector transfected cells with Hh conditioned medium treatment, Esrrb expression vector transfected cell with Hh conditioned medium treatment,
2015-11-06 | E-GEOD-71209 | biostudies-arrayexpress
Project description:Paracrine Hedgehog (Hh) signaling regulates growth and patterning in many Drosophila organs. We mapped chromatin binding sites for Cubitus interruptus (Ci), the transcription factor that mediates outputs of Hh signal transduction, and we analyzed transcription profiles of control and mutant embryos to identify genes that are regulated by Hh. Putative targets we identified include several Hh pathway components, most previously identified targets, and many targets that are novel. Analysis of expression patterns of pathway components and target genes gave evidence of autocrine Hh signaling in the optic primordium of the embryo. And, every Hh target we analyzed that is not a pathway component appeared to be regulated by Hh in a tissue-specific manner. We present evidence that Hh-dependent tissue specificity is dependent upon transcription factors that are Hh-independent, suggesting that “pre-patterns” of transcription factors partner with Ci to make Hh-dependent gene expression position-specific. We utilized the DamID method to identify regions of CiRep methylated genomic DNA in stage 10-11 Drosophila embryos.
2010-11-03 | GSE24024 | GEO
Project description:Paracrine Hedgehog (Hh) signaling regulates growth and patterning in many Drosophila organs. We mapped chromatin binding sites for Cubitus interruptus (Ci), the transcription factor that mediates outputs of Hh signal transduction, and we analyzed transcription profiles of control and mutant embryos to identify genes that are regulated by Hh. Putative targets we identified include several Hh pathway components, most previously identified targets, and many targets that are novel. Analysis of expression patterns of pathway components and target genes gave evidence of autocrine Hh signaling in the optic primordium of the embryo. And, every Hh target we analyzed that is not a pathway component appeared to be regulated by Hh in a tissue-specific manner. We present evidence that Hh-dependent tissue specificity is dependent upon transcription factors that are Hh-independent, suggesting that “pre-patterns” of transcription factors partner with Ci to make Hh-dependent gene expression position-specific. We utilized the DamID method to identify regions of CiAct methylated genomic DNA in stage 10-11 Drosophila embryos.
2010-11-03 | GSE23999 | GEO
Project description:Aberrant activation of Hedgehog pathway is responsible for initiation and maintenance of various cancers, including medulloblastoma (MB), basal cell carcinoma (BCC), and other solid and hematological tumors. Therefore, targeting Hh pathway represents promising therapeutic prospects for Hh-driven cancers. In recent years, tremendous efforts have been dedicated to the discovery of Hh pathway inhibitor. While the majority of Hh pathway inhibitors target the upstream membrane protein Smoothened (SMO). Here, we performed Next Generation Sequencing to reveal the target genes of Hh pathway by treating mouse SHH-subtype medulloblastoma cells (SmoWT) with SMO inhibitor (GDC0449) or DMSO.
2021-07-08 | GSE171689 | GEO
Project description:Purpose: This study seeks to determine whether Smarcc1 co-regulates Hedgehog (HH) target genes in the limb. Methods: To determine if Smarcc1 is required to regulate HH targets, we used genomic approaches to identify Smarcc1-regulated genes within the forelimb. We performed bulk RNA-seq on individually genotyped forelimb-bud pairs at E11.5 (39-40s) on control (2 replicates) and PrxCre/+;Smarcc1c/c (2 replicates) embryos. From this experiment we identified 928 differentially expressed genes (FDR<0.05). Results: We find that while certain HH target genes are co-regulated by SMARCC1, the majority of HH target genes do not require Smarcc1.
2024-02-03 | GSE224505 | GEO
Project description:Misactivation of the Hedgehog (Hh) pathway can cause cancers such as medulloblastomas, the most common malignant brain tumor in children, and basal cell carcinomas, the most common cancer in the United States. Hedgehog signals are transmitted through primary cilia, where Hedgehog ligands bind to Patched1 and activate Smoothened through interactions with cilia-associated sterol lipids. The gene expression programs driving cellular responses to ciliary Hh signals are incompletely understood. Thus, to define Hh target genes, we performed RNA sequencing of cells after treatment with Hh ligands (Shh, Dhh, Ihh), cilia-associated lipids (7b,27-dihydroxycholesterol, 24(S),25-epoxycholesterol), or synthetic lipids or small molecules that activate Smoothened (20(S)-hydroxycholesterol, SAG). Treatment with Hh pathway agonists identified a core gene expression program comprised of 155 genes driving lipid synthesis, metabolism, signaling, adhesion, or angiogenesis. These datasets were integrated with RNA sequencing of Hh-human medulloblastomas (n=?), a Math1-Cre SmoM2 mouse genetic model of Hh-associated medulloblastoma (n=?), and human basal cell carcinomas (n=10) to ascertain how malignant Hh signaling differs from canonical Hh signaling. We discover a conserved response to ciliary Hh signals in human or mouse medulloblastomas, including known target genes such as Gli1 or Ptch1, and novel target genes such as Hsd11b1 or Retnla. Importantly, mechanistic studies reveal Hsd11b1 to be a putative negative regulator of Hh signaling that is dysregulated in malignancies. We further demonstrate Retnla to be a positive regulator of Hh signaling that drives expression of Hsd11b2, a druggable dependency underlying Hedgehog-associated medulloblastoma. Orthotopic implantation of neuroepithelial stem cells that overexpress either Hsd11b1 and Retnla demonstrate that tumors derived Hsd11ß1 overexpression are more primitive and less aggressive whereas Retnla overexpression forms tumors that are more differentiated and behave more aggressively. In sum, we illuminate the first comprehensive transcriptome of Hh signaling and highlight the intricate interplay between Hh signaling and lipid metabolism that Hh-dependent malignancies dysregulate to drive tumor progression.
2023-06-06 | GSE233744 | GEO
Project description:Paracrine Hedgehog (Hh) signaling regulates growth and patterning in many Drosophila organs. We mapped chromatin binding sites for Cubitus interruptus (Ci), the transcription factor that mediates outputs of Hh signal transduction, and we analyzed transcription profiles of control and mutant embryos to identify genes that are regulated by Hh. Putative targets we identified include several Hh pathway components, most previously identified targets, and many targets that are novel. Analysis of expression patterns of pathway components and target genes gave evidence of autocrine Hh signaling in the optic primordium of the embryo. And, every Hh target we analyzed that is not a pathway component appeared to be regulated by Hh in a tissue-specific manner. We present evidence that Hh-dependent tissue specificity is dependent upon transcription factors that are Hh-independent, suggesting that “pre-patterns” of transcription factors partner with Ci to make Hh-dependent gene expression position-specific.
2010-11-03 | GSE24028 | GEO