Gdnf-treated murine intestinal organoids and sorted Ret+ and Ret- single cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1080653 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28108215_1.fastq.gz | Fastqsanger.gz | |||
| SRR28108215_2.fastq.gz | Fastqsanger.gz | |||
| SRR28108216_1.fastq.gz | Fastqsanger.gz | |||
| SRR28108216_2.fastq.gz | Fastqsanger.gz | |||
| SRR28108217_1.fastq.gz | Fastqsanger.gz |
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Project description:Adjacent stroma, including subepithelial fibroblasts, are believed to coordinate the differentiation process of epithelial cells, but the mechanisms are not well understood. Glial cell line-derived neurotrophic factor (GDNF) is expressed in the intestinal Pdgfra high subepithelial myofibroblasts (SEMFs), while the GDNF receptor RET is expressed in a subset of enteroendocrine cells (EECs), indicating regulatory crosstalk. In this experiment, single RET+ intestinal cells were sorted the gene expression profile was compared to non-RET cells. This provided knowledge about RET+ cell types. RET+ cells were upregulated with most of the EEC markers, indicating that RET+ cells are expressed in EECs. We also observed the differences in the gene expression profile of stromal-derived GDNF ligand on intestinal organoids. Organoids were derived from intestinal crypts of WT mice C57BL/6J and treated with 500ng/ml of Gdnf and Gfra1. GDNF-treated organoids induced the expression of EEC genes such as Pyy, Tac1, Tph1, and Cck, indicating enhanced differentiation of EC cell and L-I-N cell lineages. This highlights a stroma-epithelium crosstalk pathway regulating the differentiation of intestinal EEC subtypes.
2024-10-17 | GSE259326 | GEO
Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.<br>MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).
2013-01-17 | E-MEXP-3662 | biostudies-arrayexpress
Project description:The molecular mechanisms of endocrine resistance in breast cancer remain poorly understood. Here we used PRO-seq to map the location of hundreds of genes and thousands of distal enhancers whose activities differ between endocrine sensitive and resistant MCF-7 cells. Our genome-wide screen identified a 16-fold transcriptional increase in glial-cell line derived neurotrophic factor (GDNF), a RET tyrosine kinase receptor ligand, which is both necessary and sufficient for resistance in MCF-7 cells. GDNF causes endocrine resistance by switching the active state of a bi-stable feedback loop from ERα signaling to GDNF-RET signaling. To catalyze this switch, we found that GDNF directly downregulates ERα transcription and activates the transcription factor EGR1, which, in turn, induces GDNF expression. Remarkably, both MCF-7 cells and ER+ primary tumors appear poised for endocrine resistance via the RET signaling pathway, but lack robust RET ligand expression and only develop resistance upon expression of GDNF or other RET ligands.
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Project description:To better understand the signaling and transcriptional events involved in the GDNF-independent emergence of the ureteric bud from the Wolffian duct, microarray expression analysis was performed on embryonic kidneys from wild-type and Ret-deficient mice. Microarray data was used to identify genes and gene networks involved in the GDNF-independent outgrowth of the ureteric bud. Whole embryonic kidneys from E12.5 Ret mutant and wild-type mice were isolated. Isolated kidneys were lysed and RNA was extracted with the Qiagen RNEasy Micro kit. The RNA was amplified using the NuGEn Ovation kit and hybridized to the Affymetrix GeneChip Mouse Whole Genome 430 2.0 microarray. Three biological replicates for Ret-knockout and wild-type kidneys were performed.
2012-03-31 | E-GEOD-32093 | biostudies-arrayexpress
Project description:DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinsonâ??s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration. Comparison between DJ-1-silenced human SH-SY5Y neuroblastoma cells and control cells. Two clones were selected for each condition, and each clone was analyzed in duplicate, for a total of 8 samples.
2010-04-28 | E-GEOD-17204 | biostudies-arrayexpress
Project description:DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinson’s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.
2010-04-16 | GSE17204 | GEO
Project description:To better understand the signaling and transcriptional events involved in the GDNF-independent emergence of the ureteric bud from the Wolffian duct, microarray expression analysis was performed on embryonic kidneys from wild-type and Ret-deficient mice. Microarray data was used to identify genes and gene networks involved in the GDNF-independent outgrowth of the ureteric bud.
2012-04-01 | GSE32093 | GEO
Project description:Murine small intestinal organoids were cultured in the presence or absence of 5µM inhibitor MS023 (PubChem CID 92136227), which targets type I protein arginine methyltransferases Prmt1, Prmt3, Prmt4, Prmt6, Prmt8. Organoids were grown in culture media containing EGF, Noggin and R-spondin (ENR), media was changed after 48h, and organoids were harvested after 120h.
2020-12-16 | E-MTAB-9291 | biostudies-arrayexpress
Project description:Murine small intestinal organoids were cultured in the presence or absence of 3µM inhibitor I-CBP112 (PubChem CID 90488984), which targets E1A Binding Protein P300 (Ep300) and Creb-binding protein (Crebbp, Cbp). Organoids were grown in culture media containing EGF, Noggin and R-spondin (ENR), media was changed after 48h, and organoids were harvested after 96h.
2020-12-16 | E-MTAB-9290 | biostudies-arrayexpress
Project description:Signaling of the RET receptor is crucial for the migration, proliferation, differentiation and survival of enteric neural crest cells (ENCCs) that form the enteric nervous system (ENS). Disturbances in RET signaling are associated with ENS defects, as is seen in patients with Hirschsprung disease. However, the downstream effectors of RET signalling in ENCCs is largely unknown. This study aims to gain new insight into the pathways involved in or triggered by RET in ENCCs. We used microarrays to detect the gene expression of mouse embryonic ENCCs when we stimulated with GDNF compare to control without GDNF and also compare to the gene expression of mouse embryonic gut (all are isolated from mouse embryonic day 14.5). Our aim is to gain insight of RET-GDNF downstream effectors and also all signalling pathways that regulate by RET-GDNF in ENCCs during development. We performed gene expression profiling with RNA isolated from GDNF- (the RET ligand) stimulated and non-stimulated mouse ENCCs and also from mouse embryonic gut E14.5. We compare these three set of microarray data to each other and analyzed single-gene analysis methods. by this analysis we could detect genes that regulate by RET-GDNF signalling in ENCCs and by comparing data of ENCCs with and without GDNF to the expression data of mouse embryonic gut in the same stage of development, we could also detect gene that specifically express in ENCCs dependent and independently of RET-GDNF signalling. We analyzed the gene expression data of ENCCs with and without GDNF by gene set enrichment analysis (GSEA) to detect which pathways are down- and up-regulated by RET-GDNF signalling.
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