Gene expression profiles of islets of Langerhans isolated from 7 weeks wt and Wnt4 conditional knock outs.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE210267 | GEO | 2022/08/04
REPOSITORIES: GEO
Similar Datasets
Project description:To find the differences between β cells expressing Wnt4 and those that do not express it (or express it at low levels) at neonatal stage, murine islets at postnatal day 1 (P1) were collected. Based on a reporter expressing Cre recombinase from the Wnt4 locus, we observed that Wnt4 expression starts in a small subset of β cells at embryonic day (E) 18.5. At neonatal stages, around 50% of β cells express Wnt4 at P0 and most of cells express it by P5. We collected Wnt4 high and Wnt4 low islet cells by FACS and compared their gene expression profile. Wnt4 high islet cell population showed a significant increase of β-cell maturation and function related genes, including transcription factors such as Pdx1 and Nkx6.1, insulin 2, glucokinase (Gck), and the glucose transporter Slc2a2. On the contrary, Wnt4 low islet cell population showed significant increasing of proliferation markers such as Pcna, Mki67 and the positive cell cycle regulators Ccnd1, Ccnd3, Ccna2, Cdk1, Cdk2 and Cdk6. Taken together, these results show that Wnt4 expression is higher in more mature but less proliferative β cells.
2022-08-02 | GSE210237 | GEO
Project description:We demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is produced by both hematopoietic and non-hematopoietic cells and is both necessary and sufficient for pre-cDC1/cDC1 maintenance. Whereas BM cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss of cDC Wnt4 in CD11cCreWnt4flox/flox mice impaired differentiation of CD24+, Clec9A+, CD103+ cDC1 compared to CD11cCre controls. Conversely, sc-RNAseq analysis of BM revealed a 2-fold increase in cDC2 gene signature genes and flow cytometry demonstrated increased numbers of SIRP-α + cDC2 amid lack of Wnt4. Increased cDC2 numbers due to CD11c-restricted Wnt4 deficiency increased interleukin 5 production, group 2 innate lymphoid cell (ILC2) expansion, and host resistance to the hookworm parasite Nippostrongylus brasiliensis. Collectively, these data uncover a novel and unexpected role for Wnt4 in cDC subset differentiation and Type 2 immunity.
2019-08-01 | GSE131569 | GEO
Project description:To study the physiological role of WNT4 in the postnatal ovary, a mouse strain bearing a floxed Wnt4 allele was created and mated to the Amhr2tm3(cre)Bhr strain to target deletion of Wnt4 to granulosa cells. Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had significantly reduced ovary weights and produced smaller litters (P<0.05). Serial follicle counting demonstrated that, while Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice were born with a normal ovarian reserve and maintained normal numbers of small follicles until puberty, they had only 25.2% of the normal number of healthy antral follicles. Some Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had no antral follicles or corpora lutea and underwent premature follicle depletion. RTPCR analyses of Wnt4flox/-;Amhr2tm3(cre)Bhr/+ granulosa cells and cultured granulosa cells that overexpress WNT4 demonstrated that WNT4 regulates the expression of Star, Cyp11a1 and Cyp19, steroidogenic genes previously identified as downstream targets of the WNT signaling effector CTNNB1. WNT4- and CTNNB1-overexpressing cultured granulosa cells were analyzed by microarray for alterations in gene expression, which showed that WNT4 also regulates a series of genes involved in late follicle development and the cellular stress response via the WNT/CTNNB1 signaling pathway. Together, these data indicate that WNT4 is required for normal antral follicle development, and may act by regulating granulosa cell functions including steroidogenesis.
2009-10-23 | GSE18704 | GEO
Project description:Mice lacking the expression of Acsl1 in the heart (Acsl1H-/-) have impaired cardiac fatty acid oxidation and develop spontaneous cardiac hypertrophy due to increased mTOR activation. To explore how the loss of ACSL1 alters gene expression, we performed a global gene expression analysis on ventricular RNA isolated from Acsl1H-/- and Acsl1flox/flox mice ten weeks after tamoxifen treatment when ACSL1 protein is completely lost and the specific activity of ACSL1 in Acsl1H-/- hearts is reduced 90% Two-condition experiment, cadiac gene expression of Acsl1H-/- vs Acsl1flox/flox mice 10 weeks after tamoxifen treatment. Biological replicates: 3-4 per condition.
2014-09-29 | E-GEOD-51913 | biostudies-arrayexpress
Project description:The goal of this study was to identify genes which are differentiatlly expresesd upon induced inactivation of Rfx6 in beta cell in adult mice Rfx6fl/fl; Ins1-CreERT2 (mut) and Rfx6fl/fl (ctrl) 8 weeks old mice were injected subcutaneously with tamoxifen daily during 3 days. Pancreatic islets were isolated 5 days after the first injection and RNA purified.
2014-12-11 | E-GEOD-59622 | biostudies-arrayexpress
Project description:Our laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify a population of genes that are enriched in the renal vesicle (RV) and its derivatives using Wnt4 mutants. Experiment Overall Design: Wnt4 is required for renal vesicle (RV) induction. Therefore, RV and the derivatives (s-shaped body and eventually the mature nephron) are missing in Wnt4 mutants. At E14.5, these structures are present in wildtype kidneys. Transcriptional profile comparison between E14.5 wildtype and Wnt4 mutants therefore identify genes expressed in the RV and derivatives. Minimally pooled kidney samples were used as single biological replicates. Total RNA was isolated from these pools and subjected to a single round of amplification for use on Affymetrix arrays.
2008-06-14 | E-GEOD-6288 | biostudies-arrayexpress
Project description:Our previous studies have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is markedly induced in human primary endometrial stromal cells (HESC) as they undergo differentiation in response to steroid hormones and cAMP. WNT4 is a downstream target of BMP2 regulation in these cells. To identify the common downstream targets of BMP2 and WNT4 in human endometrial stromal cells, we performed gene expression profling of human ensometrial stromal cell transduced with BMP2 or WNT4 adenovirus. Gene expression profiling revealed that FOXO1, a forkhead family transcription factor and a known regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. These studies uncovered a linear pathway involving BMP2, WNT4, and FOXO1 that operates in human endometrium to critically control decidualization.
2013-02-08 | GSE39949 | GEO
Project description:Pancreatic beta-cell dysfunction contributes to onset and progression of type 2 diabetes. In this state beta-cells become metabolically inflexible, losing the ability to select between carbohydrates and lipids as substrates for mitochondrial oxidation. These changes lead to beta-cell dedifferentiation. We have proposed that FoxO proteins are activated through deacetylation-dependent nuclear translocation to forestall the progression of these abnormalities. However, how deacetylated FoxO exert their actions remains unclear. To address this question, we analyzed islet function in mice homozygous for knock-in alleles encoding deacetylated FoxO1 (6KR). Islets expressing 6KR mutant FoxO1 have enhanced insulin secretion in vivo and ex vivo, and decreased fatty acid oxidation ex vivo. Remarkably, the gene expression signature associated with FoxO1 deacetylation differs from wild-type by only ~2% of the > 4,000 genes regulated in response to re-feeding. But this narrow swath includes key genes required for beta-cell identity, lipid metabolism, and mitochondrial fatty acid and solute transport. The data support the notion that deacetylated FoxO1 protects beta-cell function by limiting mitochondrial lipid utilization, and raise the possibility that inhibition of fatty acid oxidation in β-cells is beneficial to diabetes treatment.
2016-05-10 | GSE77652 | GEO
Project description:Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, endogenous fibroblast TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.
2023-12-28 | GSE251976 | GEO
Project description:Our previous studies have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFM-NM-2 superfamily, is markedly induced in human primary endometrial stromal cells (HESC) as they undergo differentiation in response to steroid hormones and cAMP. WNT4 is a downstream target of BMP2 regulation in these cells. To identify the common downstream targets of BMP2 and WNT4 in human endometrial stromal cells, we performed gene expression profling of human ensometrial stromal cell transduced with BMP2 or WNT4 adenovirus. Gene expression profiling revealed that FOXO1, a forkhead family transcription factor and a known regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. These studies uncovered a linear pathway involving BMP2, WNT4, and FOXO1 that operates in human endometrium to critically control decidualization. Human endometrial stromal cells were transduced with recombinant adenovirus expressing BMP2, WNT4, or a negative control GFP at MOI 50:1 in 2 ml of culture medium. After transduction for 24 h, the viral particles were removed and the cells were treated with E+P for 3 days to induce decidualization (n=3 for each treatment), pooled total RNA from these cells was then hybridized to high density affymetrix microarrays according to the Affymetrix protocol (Human Genome HG-U133 A2.0 Array) .
2013-02-08 | E-GEOD-39949 | biostudies-arrayexpress