Multi-step Epigenetic Programming of Monocytes during Infection
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ABSTRACT:
PROVIDER: PRJNA532592 | ENA |
REPOSITORIES: ENA
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Project description:Monocytes play a major role in the defense against pathogens. They are rapidly mobilized to inflamed sites where they exert both proinflammatory and regulatory effector functions. It is still poorly understood how this dynamic and exceptionally plastic system is controlled at the molecular level. Herein, we evaluated the differentiation process that occurs in Ly6Chi monocytes during oral infection by T. gondii. Flow cytometry and single-cell analysis revealed distinct activation status and gene expression profiles in the bone marrow, the spleen and the lamina propria of infected mice. We provide further evidence that this stepwise acquisition of effector functions, such as the capacity to produce interleukin-27, is accompanied by distinct waves of epigenetic programming, highlighting a role for STAT1/IRF1 in the bone marrow and AP-1/NF-kB in the periphery. This work broadens our understanding of the molecular events that occur in vivo during monocyte differentiation in response to inflammatory cues.
2019-12-31 | GSE129724 | GEO
Project description:A multi-step transcriptional and chromatin cascade underlies motor neuron programming
| PRJNA319035 | ENA
Project description:Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process.
2016-12-07 | GSE80561 | GEO
Project description:Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process.
2016-12-07 | GSE80511 | GEO
Project description:Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process.
2016-12-07 | GSE80321 | GEO
Project description:Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process.
2016-12-07 | GSE80482 | GEO
Project description:Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process.
2016-12-07 | GSE81275 | GEO
Project description:Single-cell Transcriptomics reveals multi-step adaptations to endocrine therapy
| PRJNA506208 | ENA
Project description:Non-specific protective effects against reinfection have been described following infection with Candida albicans. Here we show that mice defective in functional T and B lymphocytes were protected against reinfection with C. albicans in a monocyte-dependent manner. C. albicans and beta glucans induced functional programming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the beta glucan receptor dectin 1 and the non-canonical Raf 1 pathway. Monocyte training by beta-glucans was mediated by epigenetic mechanisms through genome-wide changes in histone trimethylation at H3K4. Pathway analysis showed specific induction of epigenetic changes in genes of innate immunity. The functional programming of monocytes, reminiscent of similar properties of NK cells, has been termed M-bM-^@M-^\trained immunityM-bM-^@M-^] and may be employed for the design of improved vaccination strategies. Chromatin-IP at day7 followed by highthroughput sequencing to look at the differences in H3K4me3 and H3K27me3 binding in Monocytes either cultured in RPMI only versus those trained for 24hrs with beta glucan. Additionally expression analysis was performed by doing strandspecific RNAseq also for both unstimulated and beta glucan trained monocytes for correlating the histone modification changes with the expression changes. Biological replicates were generated from independent samples for H3K4me3 and RNAseq. Additional H3K4me3 ChIP-seq assays were performed for day0 untreated, 24hrs control and beta glucan trained monocytes. H3K4me3 ChIP-seq was also performed for Mouse macrophages both saline(control) and low dose Candida treated.
2012-12-21 | E-GEOD-34260 | biostudies-arrayexpress
Project description:Time-dependent regulation of cellular programming of monocytes by NCOR2
| PRJNA379442 | ENA