Hedgehog signaling affects platelet-derived growth factor signaling mediated alveolar septum formation during postnatal lung development [bulk RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207051 | GEO | 2023/01/26
REPOSITORIES: GEO
Similar Datasets
Project description:HH inhibition reproduces the lung phenotype of PDGF pathway knockout lungs and results in profound effects on differentiation and gene expression of Pdgfra-expressing alveolar mesenchymal cells, in particular myofibroblasts.
2023-01-26 | GSE207061 | GEO
Project description:Deregulated accumulation of myofibroblasts (MF) is central to liver fibrosis pathogenesis, but the mechanisms controlling myofibroblast fate remain poorly understood. Here we investigated whether Hedgehog (Hh) signaling regulates MF fate by modulating MF metabolism. We performed microarrays to screen hepatic stellate cells (HSC) for transition-associated changes in metabolism. To capture early and late events in their MF transition process, we compared gene expression in freshly isolated primary HSC with gene expression in the same cells after 7 days in culture. We analyzed total RNA from 3 replicates of HSC in the early transition or quiescent state (n=3) as well as in the late phase of transition (MF) (n=3).
2012-12-31 | E-GEOD-34949 | biostudies-arrayexpress
Project description:Aberrant activation of Hedgehog (HH) signaling has been identified as a key etiologic factor of many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling profoundly depend on interactions with other pathways such as epidermal growth factor receptor-mediated signaling which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. We demonstrate that the human medulloblastoma cell line Daoy possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic Hedgehog or Smoothened agonist induced expression of GLI1 protein and prevented processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed on the transcriptomic as well as proteomic level. Daoy cells responded to the co-treatment by downregulating GLI1, PTCH, and HHIP on the transcript level which was also seen when Amphiregulin (AREG) was used instead of EGF. The finding that EGFR signaling silences proteins acting as negative regulators of HH signaling is firstly described here as a novel crosstalk mechanism. Furthermore, combined EGFR/HH signaling maintains high GLI1 protein levels contrasting its downregulation on the transcript level. On the other hand, high level synergism was observed with respect to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile pointing to more wide-spread, yet context-dependent, interactions between HH/GLI and growth factor receptor signaling in human malignancies. To study interactions between HH- and EGF-induced signaling, time-resolved measurements were carried out over a period of 24 h at 14 different time points after stimulation by EGF with and without additional stimulation by SHH. Furthermore, as a control, cells without any stimulation by EGF and SHH (control) and cells in the presents of SHH were analyzed. Overall, three biological replicates of 60 different treatment/timepoints were analyzed yielding 180 different samples.
2014-07-31 | E-GEOD-46045 | biostudies-arrayexpress
Project description:To compare the gene expression profiles between normal and Pdgfra deficient secondary crest myofibroblasts (SCMF). There was a total of 1808 differentially expressed genes of which 866 increased, while 942 decreased in the Pdgfra deficient SCMFs. The differentially expressed genes are related to multiple functions of SCMFs. Pdgfra plays an important role in multiple functions, especially elastogenesis, of secondary crest myofibroblasts during alveolar formation.
2019-02-13 | GSE126457 | GEO
Project description:Deregulated accumulation of myofibroblasts (MF) is central to liver fibrosis pathogenesis, but the mechanisms controlling myofibroblast fate remain poorly understood. Here we investigated whether Hedgehog (Hh) signaling regulates MF fate by modulating MF metabolism. We performed microarrays to screen hepatic stellate cells (HSC) for transition-associated changes in metabolism. To capture early and late events in their MF transition process, we compared gene expression in freshly isolated primary HSC with gene expression in the same cells after 7 days in culture.
2012-12-31 | GSE34949 | GEO
Project description:Aberrant activation of Hedgehog (HH) signaling has been identified as a key etiologic factor of many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling profoundly depend on interactions with other pathways such as epidermal growth factor receptor-mediated signaling which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. We demonstrate that the human medulloblastoma cell line Daoy possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic Hedgehog or Smoothened agonist induced expression of GLI1 protein and prevented processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed on the transcriptomic as well as proteomic level. Daoy cells responded to the co-treatment by downregulating GLI1, PTCH, and HHIP on the transcript level which was also seen when Amphiregulin (AREG) was used instead of EGF. The finding that EGFR signaling silences proteins acting as negative regulators of HH signaling is firstly described here as a novel crosstalk mechanism. Furthermore, combined EGFR/HH signaling maintains high GLI1 protein levels contrasting its downregulation on the transcript level. On the other hand, high level synergism was observed with respect to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile pointing to more wide-spread, yet context-dependent, interactions between HH/GLI and growth factor receptor signaling in human malignancies.
2014-07-31 | GSE46045 | GEO
Project description:Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk.
2016-12-07 | GSE75760 | GEO
Project description:Osteoarthritis (OA) is a common degenerative disease of the joint. Data from our lab indicates that Hedgehog (Hh) signaling is activated in human OA and murine models of OA (Lin et al., 2009, Nature Medicine). To identify Hh target genes, microarray analyses were performed to detect changes in gene expression when the Hh pathway was inhibited in human OA cartilage samples. Identifying Hh target genes in chondrocytes will elucidate key regulatory networks that govern chondrocyte homeostasis and provide novel therapeutic strategies for OA.
2016-05-20 | GSE54749 | GEO
Project description:The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or over-activation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as RBPJ- and Smo-deficiency do not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression “signature”. Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that the Hh pathway can be targeted in future clinical trials addressing the effect of Hh inhibition on leukemia-initiating cell maintenance. Transcriptional consequences of inactivating Smo (hh loss-of-function) in LKS cells.
2009-03-11 | GSE15194 | GEO
Project description:Despite Hedgehog’s influence on T-cell activation and proliferation, the transcriptional targets of Gli2 in lymphocytes are not known. We therefore examined the Hedgehog-dependent transcriptional response of resting and early-stage activated T-cells in order to define their transcriptional response to Hedgehog pathway activation. We have established transgenic models where transcription of target genes by Gli2 is either constitutively activated or repressed in cells of the T-lineage. Gli2 has an N-terminal repressor domain and a C-terminal activator domain. Lck-Gli2?N2 (Gli2A) mice carry a transgene encoding a truncated form of Gli2 that acts as a permanent transcriptional activator of Hh target genes. Conversely, Lck-Gli2?C2 (Gli2R) mice express a repressor of Gli2-dependent transcription, which by binding to Gli binding sites inhibits physiological Hh-dependent transcription, and hence Hh signal transduction, in the cell. These transgenes are driven by the Lck promoter and are only expressed in T-lineage cells Purified fresh, resting CD4 cells (unstimulated) and from CD4 cells stimulated with anti-CD3/CD28 for 6h (stimulated) were analysed in order to obtain transcriptional profiles before and during the early stages of T-cell activation.
2013-01-01 | E-GEOD-33156 | biostudies-arrayexpress