Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-01 | GSE231406 | GEO
Project description:IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs - additional datasets
| PRJNA1107149 | ENA
Project description:IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs
| PRJNA964768 | ENA
Project description:Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-overexpressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation.
| S-EPMC4158926 | biostudies-literature
Project description:The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using high-dimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+DC) heterogeneity originates from two distinct pathways of development. The lymphoid-primed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency.
| S-EPMC7447982 | biostudies-literature
Project description:Microglia are resident immune cells in the central nervous system, including the retina that surveil the environment for damage and infection. Following retinal damage, microglia undergo morphological changes, migrate to the site of damage, and express and secrete pro-inflammatory signals. In the zebrafish retina, inflammation induces the reprogramming and proliferation of Müller glia and the regeneration of neurons following damage or injury. Immunosuppression or pharmacological ablation of microglia reduce or abolish Müller glia proliferation. We evaluated the retinal architecture and retinal regeneration in adult zebrafish irf8 mutants, which have significantly depleted numbers of microglia. We show that irf8 mutants have normal retinal structure at 3 months post fertilization (mpf) and 6 mpf but fewer cone photoreceptors by 10 mpf. Surprisingly, light-induced photoreceptor ablation induced Müller glia proliferation in irf8 mutants and cone and rod photoreceptor regeneration. Light-damaged retinas from both wild-type and irf8 mutants show upregulated expression of mmp-9, il8, and tnfβ pro-inflammatory cytokines. Our data demonstrate that adult zebrafish irf8 mutants can regenerate normally following acute retinal injury. These findings suggest that microglia may not be essential for retinal regeneration in zebrafish and that other mechanisms can compensate for the reduction in microglia numbers.
| S-EPMC11362524 | biostudies-literature
Project description:Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. The integration of gene expression, DNA methylation, and chromatin state dynamics reveals that stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Erythroid-specific, nonpromoter sites of chromatin accessibility are linked to erythroid cell phenotypic variation and inherited disease. Comparative analyses of stage-specific chromatin accessibility indicate that there is limited early chromatin priming of erythroid genes during hematopoiesis. The epigenome of terminally differentiating erythroid cells defines a distinct subset of highly specialized cells that are vastly dissimilar from other hematopoietic and nonhematopoietic cell types. These epigenomic and transcriptome data are powerful tools to study human erythropoiesis.
| S-EPMC6863094 | biostudies-literature
Project description:This is the first study to our knowledge to report a novel mutation in the interferon regulatory factor 8 gene (IRF8G388S ) associated with multiple idiopathic tooth root resorption, a form of periodontal disease. The IRF8G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. Functional assays demonstrated that the IRF8G388S mutant promoted osteoclastogenesis and failed to inhibit NFATc1-dependent transcriptional activation when compared with IRF8WT control. Further, similar to subjects with heterozygous IRF8G388S mutation, Irf8+/- mice exhibited increased osteoclast activity in the mandibular alveolar bone surrounding molar teeth. Immunohistochemistry illustrated increased NFATc1 expression in the dentoalveolar region of Irf8-/- and Irf8+/- mice when compared with Irf8+/+ controls. Genomewide analyses revealed that IRF8 constitutively bound to regulatory regions of several thousand genes in osteoclast precursors, and genetic aberration of IRF8 significantly enhanced many osteoclast-specific transcripts. Collectively, this study delineates the critical role of IRF8 in defining osteoclast lineage and osteoclast transcriptional program, which may help in better understanding of various osteoclast-mediated disorders, including periodontal disease. © 2019 American Society for Bone and Mineral Research.
| S-EPMC6663587 | biostudies-literature
Project description:The largest diversity of neural lineages generated from the subventricular zone (SVZ) occurs early after birth and is regulated in a spatiotemporal manner depending on the expression of specific transcriptional cues. Transcriptomics and fate-mapping approaches were employed to explore the relationship between regional expression of transcription factors by neural stem cells (NSCs) and the specification of distinct neural lineages. Our results support an early priming of NSCs for the genesis of defined cell types depending on their spatial location in the SVZ and identify HOPX as a marker of a subpopulation primed toward astrocytic fates. Manipulation of HOPX expression, however, showed no effect on astrogenesis but resulted in marked changes in the number of NSCs and of their progenies. Taken together, our results highlight transcriptional and spatial heterogeneity of postnatal NSCs and reveal a key role for HOPX in controlling SVZ germinal activity.
| S-EPMC6135899 | biostudies-literature
Project description:Microglial cells are involved in surveillance and cleaning of the central nervous system. Recently, microglial-like cells (MLC) have been found in an adult cochlea and investigated for their role in cochlear inflammation. The presence and potential roles of MLCs during the development of the cochlea, however, remain unclear. In this study, immunostaining was performed using the MLC-specific marker IBA1 to characterize the presence, distribution, and morphology of MLCs in the developing cochlea. From P0 to P14, MLCs were present in a variety of cochlear regions including the modiolus, spiral lamina, spiral ganglion, spiral ligament, and the organ of Corti. Interestingly, the overall number of MLCs in a mouse cochlea steadily increased since P0, peaks at P5, then gradually decreased from P5 to P14. In the spiral ligament, the distribution of the MLCs trends to shift from the type I/II fibrocyte-rich regions to the type III/IV fibrocyte-rich regions during the course of cochlear development, accompanied by the morphological changes of MLCs from the amoeboid, activated form to the ramified, quiescent form. Our results suggested that MLCs experience drastic morphological and distributional changes during postnatal cochlear development, which may play a role in the maturing and remodeling of the cochlea.
| S-EPMC6091412 | biostudies-literature