Inducible intestinal epithelial knockout of PRMT1 in mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE263245 | GEO | 2025/05/12
REPOSITORIES: GEO
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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.
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Project description:Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity and systemic metabolism and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences with murine EECs, including in hormones, sensory receptors and transcription factors. Notably, several novel hormone-like molecules were identified. Inter-EEC communication is exemplified by Secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.
2020-05-15 | PXD017468 | Pride
Project description:PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. We generated T. gondii mutants lacking PRMT1 (∆prmt1) by deletion of the PRMT1 gene. ∆prmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the complemented strain ∆prmt::PRMT1mRFP. PRMT1 localizes primarily in the cytoplasm with enrichment at the centrosome, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, ∆prmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole genome expression profiling demonstrated differences in expression of cell cycle regulated genes in ∆prmt1 relative to the complemented ∆prmt1::PRMT1mRFP and parental wild-type strains, but these changes did not correlate with a specific block in cell cycle. Although PRMT1’s primary biological function was previously proposed to be methylation of histones, our genetic studies suggest that the most critical function of PRMT1 is within the centrosome as a regulator of daughter cell counting to assure the proper replication of the parasite. RNA samples were isolated in triplicates from RH-hxgprt parent strain (W), PRMT1 knockout (K) strain and PRMT1 knockout strain complemented with RFP-tagged PRMT1 protein (C). Parasites were grown for 32h at 37C. Samples were hybridized to the Toxoplasma gondii Affymetrix microarray (ToxoGeneChip: http://ancillary.toxodb.org/docs/Array-Tutorial.html). Hybridization data was preprocessed with Robust Multi-array Average (RMA) and normalized using per chip and per gene median polishing and analyzed using the software package GeneSpring GX (Agilent Technologies).
2015-09-18 | E-GEOD-73177 | biostudies-arrayexpress
Project description:Analysis of FACS-sorted intestinal Neurog3+/+ and Neurog3+/- cells from Neurog3 fluorencent reporter mice carrying two-(+/+) or one- (+/-) Neurog3 alleles. In the intestine, Neurog3 is an enteroendocrine (EE) lineage determinating transcription factor that transiently expressed in early EEC progenitors. By comparison the molecular profiles of Neurog3+/+ and Neurog3+/- cells, we hypothesized that Neurog3 gene dosage regulates the allocation of EE progenitor fates towards EEC vs. goblet cells.
2020-08-13 | GSE149203 | GEO
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117099 | GEO
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117097 | GEO
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117096 | GEO
Project description:Intestinal crypts isolated from Apcflox/flox; villin-CreERT mice were treated with Tamoxifen to induce the deletion of Apc. Tamoxifen-treated organoids were selected in the absence of Wnt agonists and then treated with TGF-beta. Total RNA obtained from Tamoxifen-treated, Apc-deleted intestinal organoids in the absence or presence of 3 ng/ml TGF-beta (18h).
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Project description:Transcriptional deregulation plays a major role in acute myeloid leukemia, identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence showing the functional involvement and therapeutic potentials of targeting PRMT1 with H4R3 methyltransferase activity in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C with H3K9 demethylase activity by chimeric transcription factors to mediate epigenetic reprogramming. Inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a novel and targetable epigenetic circuitry mediated by PRMT1 and KDM4C in acute leukemia.
2016-01-14 | E-MTAB-3322 | biostudies-arrayexpress
Project description:Intestinal crypts isolated from Apcflox/flox; villin-CreERT mice were treated with Tamoxifen to induce the deletion of Apc. Tamoxifen-treated organoids were selected in the absence of Wnt agonists and then treated with TGF-beta.
2014-04-18 | GSE35093 | GEO