RACK1 prevents premature differentiation of epidermal progenitors by inhibiting IRF6 expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE181265 | GEO | 2021/11/10
REPOSITORIES: GEO
Similar Datasets
Project description:RACK1 prevents premature differentiation of epidermal progenitors by inhibiting IRF6 expression
| PRJNA751366 | ENA
Project description:The integrity of the mammalian epidermis is essential for organism survival, and it depends on a balance of proliferation and differentiation in the resident stem cell population. The kinase Ripk4 and the transcription factor Irf6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft tissue fusions, resulting in neonatal lethality. However, the mechanism by which these genes control epidermal differentiation in vivo is unknown. By generating various mouse knock-out and knock-in strains we demonstrate that in vivo the role of Ripk4 in development is dependent on its kinase activity, Ripk4 and Irf6 function cell autonomously in the epidermis,Ripk4 and Irf6 lie on a linear pathway and phosphorylation of Irf6 on Serine413 and Serine424 is essential to prime it for activation. This priming then allows Ripk4 to phosphorylate Irf6 on Serine90, which ensures Irf6 activation. We then use RNA-seq, ChIP-seq and ATAC-seq analysis to define the global transcriptional targets of Irf6 in epidermal differentiation. Collectively, our results explain how Ripk4 activates Irf6, and how this pathway ensures epidermal differentiation and a functional barrier. This is crucial for understanding the etiology of developmental syndromes that are characterized by orofacial, skin and genital abnormalities.
2019-08-29 | GSE124047 | GEO
Project description:IRF2, IRF6, and MYB are candidate regulators of human erythropoiesis. We here examine primary CD34+ hematopoietic stem/progenitor cells (HSPCs)-derived erythroid progenitors with control, IRF2, IRF6, or MYB shRNA lentiviral transduction prior to differentiation. Gene expression microarray profiling datasets for MYB shRNA and control shRNA were obtained from Gene Expression Omnibus (GEO) under accession number GSE25678. The data were analyzed together with the datasets obtained in this study. Primary maturing adult erythroblasts were generated ex vivo from CD34+ hematopoietic stem/progenitor cells (HSPCs) using a serum-free two-phase liquid culture system. CD34+ HSPCs were transduced with lentiviruses containing shRNAs against IRF2 or IRF6 gene, selected and differentiated to proerythroblasts (ProEs). Cells were harvested at day 5 of differentiated and total RNA were extracted. This was used to hybridize to Affymetrix expression arrays using the HG-U133 Plus 2.0 platform.
2012-10-05 | E-GEOD-36988 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) regulate plant development by post-transcriptional regulation of target genes. In Arabidopsis thaliana, DCL1 processes precursors (pri-miRNAs) to miRNA duplexes, which associate with AGO1. Additional proteins act in concert with DCL1 (e.g. HYL1 and SERRATE) or AGO1, respectively, to facilitate efficient and precise pri-miRNA processing and miRNA loading. In this study, we show that the accumulation of plant microRNAs depends on RECEPTOR FOR ACTIVATED C KINASE 1 (RACK1), a scaffold protein found in all higher eukaryotes. miRNA levels are reduced in rack1 mutants and our data suggest that RACK1 affects the microRNA pathway via several distinct mechanisms involving direct interactions with known microRNA factors: RACK1 ensures the accumulation and processing of some pri-miRNAs, directly interacts with SERRATE and is part of an AGO1 complex. As a result, mutations in RACK1 lead to misregulation of miRNA target genes, which is important for ABA responses and phyllotaxy. In conclusion, our study discovered complex functioning of RACK1 proteins in the Arabidopsis miRNA pathway, which are important for miRNA production and therefore plant development.
2013-07-01 | GSE40579 | GEO
Project description:We found that Rack1 increased in microglia in AD mouse model. Conditional knockout of Rack1 in microglia reduced Aβ aggregation, alleviated neuroinflammation, and rescued cognitive impairments in AD mouse model. Mechanism investigation revealed that knockout of Rack1 in microglia decreased microglial numbers but increased astrocytic numbers and phagocytic activities via IGF1-IGF1R signaling.
2024-06-30 | GSE256191 | GEO
Project description:MicroRNA microarray profiling analysis was performed on human gastric cancer AGS cells after RACK1 silenced or not
2016-03-01 | E-MTAB-2619 | biostudies-arrayexpress
Project description:MicroRNA microarray profiling analysis was performed on human gastric cancer HGC cells after RACK1 silenced or not
2016-03-01 | E-MTAB-3484 | biostudies-arrayexpress
Project description:The integrity of the mammalian epidermis is essential for organism survival, and it depends on a balance of proliferation and differentiation in the resident stem cell population. The kinase Ripk4 and the transcription factor Irf6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft tissue fusions, resulting in neonatal lethality. However, the mechanism by which these genes control epidermal differentiation in vivo is unknown. By generating various mouse knock-out and knock-in strains we demonstrate that in vivo the role of Ripk4 in development is dependent on its kinase activity, Ripk4 and Irf6 function cell autonomously in the epidermis,Ripk4 and Irf6 lie on a linear pathway and phosphorylation of Irf6 on Serine413 and Serine424 is essential to prime it for activation. This priming then allows Ripk4 to phosphorylate Irf6 on Serine90, which ensures Irf6 activation. We then use RNA-seq, ChIP-seq and ATAC-seq analysis to define the global transcriptional targets of Irf6 in epidermal differentiation. Collectively, our results explain how Ripk4 activates Irf6, and how this pathway ensures epidermal differentiation and a functional barrier. This is crucial for understanding the etiology of developmental syndromes that are characterized by orofacial, skin and genital abnormalities.
2019-08-29 | GSE127341 | GEO
Project description:The integrity of the mammalian epidermis is essential for organism survival, and it depends on a balance of proliferation and differentiation in the resident stem cell population. The kinase Ripk4 and the transcription factor Irf6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft tissue fusions, resulting in neonatal lethality. However, the mechanism by which these genes control epidermal differentiation in vivo is unknown. By generating various mouse knock-out and knock-in strains we demonstrate that in vivo the role of Ripk4 in development is dependent on its kinase activity, Ripk4 and Irf6 function cell autonomously in the epidermis,Ripk4 and Irf6 lie on a linear pathway and phosphorylation of Irf6 on Serine413 and Serine424 is essential to prime it for activation. This priming then allows Ripk4 to phosphorylate Irf6 on Serine90, which ensures Irf6 activation. We then use RNA-seq, ChIP-seq and ATAC-seq analysis to define the global transcriptional targets of Irf6 in epidermal differentiation. Collectively, our results explain how Ripk4 activates Irf6, and how this pathway ensures epidermal differentiation and a functional barrier. This is crucial for understanding the etiology of developmental syndromes that are characterized by orofacial, skin and genital abnormalities.
2019-08-29 | GSE127338 | GEO
Project description:Transcription factor Pax5 activates genes essential for B-cell development and function. However, the regulation of Pax5 expression remains elusive. Adaptor Rack1 can interact with multiple transcription factors and modulate their activation and/or stability. Despite that, its role in the transcriptional control of B-cell fates is largely unknown. Here we show that CD19-driven Rack1 deficiency leads to pro-B accumulation and simultaneous reduction of B cells at later developmental stages. The generation of bone marrow chimeras indicates a cell-intrinsic role of Rack1 in B-cell homeostasis. Moreover, Rack1 augments BCR and TLR signaling in mature B cells. Based on diminished CD19 expression upon Rack1 deficiency, further exploration reveals that Rack1 maintains Pax5 protein levels through direct interaction and consequent prevention of Pax5 ubiquitination. Accordingly, Mb1-driven Rack1 deficiency almost completely blocks B-cell development at the pro-B cell stage. Thus, Rack1 regulates B-cell development and function through, at least partially, binding to and stabilizing Pax5.
2024-11-06 | GSE273420 | GEO