Nox4-IGF2 axis promotes differentiation of embryoid body cells into derivatives of the three embryonic germ layers
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ABSTRACT:
PROVIDER: PRJNA750064 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15262863_1.fastq.gz | Fastqsanger.gz | |||
| SRR15262863_2.fastq.gz | Fastqsanger.gz | |||
| SRR15262864_1.fastq.gz | Fastqsanger.gz | |||
| SRR15262864_2.fastq.gz | Fastqsanger.gz | |||
| SRR15262865_1.fastq.gz | Fastqsanger.gz |
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Project description:Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellular processes including differentiation of stem cells. We identified Nox4 as the major ROS generating enzyme whose expression is induced during differentiation of embryoid body (EB) into cells of all three germ layers. The role of Nox4 was examined using iPS cells generated from Nox4 -/- mouse. Differentiation markers showed significantly reduced expression levels consistent with the importance of Nox4-generated ROS during this process. From transcriptomic analyses, we found insulin-like growth factor 2 (IGF2), a member of a gene family extensively involved in embryonic development, as one of the most down-regulated genes. Indeed, addition of IGF2 to culture partly restored the differentiation efficiency of Nox4-/- iPS cells. Our results reveal an important signaling axis mediated by ROS in control of crucial events during differentiation of pluripotent stem cells.
2021-07-28 | GSE180912 | GEO
Project description:Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellular processes including differentiation of stem cells. We identified Nox4 as the major ROS-generating enzyme whose expression is induced during differentiation of embryoid body (EB) into cells of all three germ layers. The role of Nox4 was examined using induced pluripotent stem cells (iPSCs) generated from Nox4 knockout (Nox4-/-) mouse. Differentiation markers showed significantly reduced expression levels consistent with the importance of Nox4-generated ROS during this process. From transcriptomic analyses, we found insulin-like growth factor 2 (IGF2), a member of a gene family extensively involved in embryonic development, as one of the most down-regulated genes in Nox4-/- cells. Indeed, addition of IGF2 to culture partly restored the differentiation competence of Nox4-/- iPSCs. Our results reveal an important signaling axis mediated by ROS in control of crucial events during differentiation of pluripotent stem cells.
| S-EPMC8942977 | biostudies-literature
Project description:We report the function of IGF2 in regulating the differentiation of ESCs, and then we performed RNA-seq for the wild-type and Igf2 knockout ESCs and embryoid bodies collected at different time points to analyze the transcriptomes. The results showed a significant difference between wild-type and Igf2 knockout groups in transcriptomes, and we performed a series experiments to study the function of Igf2 in the differentiation of ESCs.
2021-07-09 | GSE173810 | GEO
Project description:Transcriptomic analysis of cardiomyocytes in NOX4 transgenic mice
2014-06-01 | E-MEXP-3161 | biostudies-arrayexpress
Project description:Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-β-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-β in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-β treatment, Nox4 did not influence skin myofibroblast differentiation. Nevertheless, up-regulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3, as well as down-regulation of Islr were observed in Nox4-deficient fibroblasts. Altogether, we provide extensive evidence challenging a profibrotic role of NOX4 in skin fibroblasts and show that Nox4 regulates Ucp2 and Hddc3 expression, suggesting the presence of a so far undescribed redox crosstalk between NOX4 and redox homeostasis in fibroblasts.
2023-03-15 | GSE197562 | GEO
Project description:Gene expression profiling of mouse articular chondrocytes infected with Ad-C or Ad-Nox4 In this study, we have attempted to explore the effects of Nox4 and have identified numerous genes which are involved in osteoarthritis pathogenesis.
2022-03-01 | GSE146272 | GEO
Project description:Within the family of NADPH oxidases, Nox4 is unique as it is predominantly localized in the endoplasmic reticulum, has constitutive activity and generates H2O2. We hypothesize that these features are consequences of a so far unidentified Nox4-interacting protein. Interacting proteins were screened by quantitative SILAC-Co-immunoprecipitation in HEK293 cells stably overexpressing Nox4. By this technique, several interacting proteins were identified with calnexin showing the most robust interaction.
2016-02-17 | PXD003514 | Pride
Project description:Embryonic stem (ES) cells, when grown in suspension culture without feeders, spontaneously form round structures known as embryoid bodies. Given the appropriate conditions, these cells can differentiate over time into precursors of all three germ layers. Embryoid bodies, in a disorganized way, mimic early embryonic development to a certain extent and can be used as a synchronously differentiating large scale source of tissue for the study of biological determinants of early differentiation. Embryoid bodies have been used as a source for most early protocols that derive specific differentiated cell types from undifferentiated ES cells, although some protocols, notably those that derive neurons from ES cells, have moved on from EBs as a result of varying replicability and yield. We have decided to look at the transcriptomic profiles of embryoid bodies during the initial stages of embryoid body formation and differentiation, in order to pinpoint novel determinants of key developmental stages. Keywords: time course
2007-08-15 | GSE8766 | GEO
Project description:Within the family of NADPH oxidases, Nox4 is unique as it is predominantly localized in the endoplasmic reticulum, has constitutive activity and generates H2O2. We hypothesize that these features are consequences of a so far unidentified Nox4-interacting protein. Blue native gel electrophoresis of solubilized membranes from HEK293 cells (overexpressing Nox4) separated macromolecular complexes containing Nox4. The combination of native gel electrophoresis and quantitative mass spectrometry was applied to identify proteins that co-migrate with Nox4. In addition, the data set contains information about macromolecular protein complexes in human cellular membranes that are stable to the solubilization with digitonin.
2017-04-07 | PXD003509 | Pride
Project description:Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole body Nox4 knockout mice (Nox4-/-) and conditional knockout (CKO) mice with depletion of Nox4 in the limb bud mesenchyme compared with those from control mice (Nox4fl/fl), but they were reversed after 9 passages. In both sexes, bone volume, trabecular number and bone mineral density were significantly lower in 3-week old CKO and Nox4-/- mice compared with Nox4fl/fl controls. This was reflected in serum levels of bone formation markers alkaline phosphatase (ALP) and procollagen 1 intact N-terminal propeptide (P1NP). However, under-developed bone formation in 3-week old CKO and Nox4-/- mice quickly caught up to levels of control mice by 6-week of age, remained no different at 13-week of age, and was reversed in 32-week old male mice. Osteoclastogenesis showed no differences among groups, however, CTX1 reflecting osteoclast activity was significantly higher in 3-week old male CKO and Nox4-/- mice compared with control mice, and significantly lower in 32-week old Nox4-/- mice compared with control mice. These data suggest that Nox4 expression and ROS signaling in bone and osteoblastic cells coordinately play a role on osteoblast differentiation, proliferation and maturation.
2022-06-22 | GSE195454 | GEO