Project description:The lineage-determining transcription factor IRF8's function in microglia is unclear. Our study aims to shed light on this by analyzing the genome-wide, temporal transcriptome profiles of wild-type and IRF8KO microglia. We used deep-sequencing and differential analysis to identify the effects of IRF8 on transcription programs in microglia, such as microglia identity gene expression. This study provides a new understanding of the transcriptional programs in microglia.
Project description:The role of the lineage-determining transcription factor IRF8 in microglia remains unelucidated. We report the genome-wide, transcriptome profiles of wild-type, IRF8KO, IRF8cKO, Batf3KO, 5xFAD, and 5xFAD/IRF8KO microglia. Deep-sequencing and subsequent differential analysis revealed the impacts of IRF8 on microglia-specific transcription programs, such as cell identity. Sall1 and Batf3 genes were identified as a downstream transcription factor of IRF8, and Batf3 dependent genes showed correlation with IRF8-dependent genes in microglia. The conditional depletion of IRF8 gene after microglial maturation (P14) increased or decreased the gene expression, most of which were shared with those of IRF8KO. This study provides a novel insight into understanding transcriptional programs in microglia.
Project description:The role of the lineage-determining transcription factor IRF8 in microglia remains unelucidated. We analyzed the transcriptome diversity of wild-type and IRF8KO microglia. Deep-sequencing and subsequent differential analysis revealed the significance of the IRF8-dependent transcription on microglial heterogeneity and self-renewing. This study provides a novel insight into understanding IRF8-mediated transcriptional programs in microglia.
Project description:The role of the lineage-determining transcription factor, Interferon regulatory factor (IRF8), in microglia remains elucidated. We report the genome-wide methyl-CpG status in adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia by whole-genome bisulfite-Seq (WGBS). Deep-sequencing and subsequent differential analysis revealed that IRF8KO microglia exhibited a cell-intrinsic methylation profile. Furthermore, the differentially methylated regions showed a significant correlation with IRF8-dependent chromatin accessibility in microglia. This study provides a novel insight into understanding epigenetic regulation in microglia.
Project description:The role of a transcription factor, Interferon Regulatory Factor 8 (IRF8), in microglia is yet to be fully understood. We conducted a study to examine the chromatin status of postnatal and adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia through ATAC-Seq. We also added 5xFAD Alzheimer's disease microglia to observe any chromatin events that may be similar in disease-associated microglia. After deep-sequencing and differential analysis, we discovered that chromatin accessibility in microglia is dependent on IRF8. In the absence of IRF8, there was aberrant chromatin accessibility that potentially resulted in mRNA transcription of genes that were upregulated in IRF8KO microglia, which was distinct from 5xFAD microglia. This study contributes to a better understanding of epigenetic regulation in microglia.
Project description:The role of the lineage-determining transcription factor, Interferon regulatory factor (IRF8), in microglia remains unelucidated. We report the genome-wide chromatin status in adult wild-type (WT) and IRF8-knockout (IRF8KO) microglia by ATAC-Seq. Deep-sequencing and subsequent differential analysis revealed that chromatin accessibility in microglia requires IRF8. At the same time, the loss of IRF8 gains aberrant chromatin accessibility that potentially confers mRNA transcription of the genes upregulated in IRF8KO microglia. This study provides a novel insight into understanding epigenetic regulation in microglia.
Project description:IRF8 is a transcription factor that is crucial in determining the lineage of microglia. We previously showed that IRF8 is robustly bound during the early postnatal period. To better understand IRF8's postnatal functions, we analyzed mice in which IRF8 was removed after P16. By using single-cell nuclei sequencing, we analyzed cells in which IRF8 was definitely knocked out and investigated both the transcriptome and chromatin accessibility that IRF8 regulates. The differential analysis showed the importance of IRF8 in regulating postnatal transcriptional programs and epigenetic landscapes that are related to microglial identity and disease-associated genes. This study provides a new perspective on how IRF8-mediated transcriptional programs affect microglia.