) and merged with data of odds ratios of MS risk to generate risk SNP and susceptibility gene pairs. Pairs of SNPs and genes with missing expression profiles were excluded from the analysis. A list of 539 pairs of SNPs and genes was generated . If the MS risk allele showed higher expression of the corresponding susceptibility gene showed lower expression of the corresponding susceptibility gene , that gene was defined as a protective MS gene .
In order to estimate enrichment of differentially expressed genes in pre-determined MS gene sets, we used a simulation method. We determined DEGs in two donors with the shRNA that effectively knocked down DDX39B, Sh3, based on the Gfold method with a cutoff of Gfold value change >0.3. The observed number of DEGs found in the MS gene set, k, was calculated by intersecting DEGs with each MS gene set . We then calculated enrichment using a resampling method.
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Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing - Journal of NeuroinflammationBackground Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis. Method In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope. Results We showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states. Conclusion In all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.
Source: BioMedCentral - 🏆 22. / 71 Read more »
Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing - Journal of NeuroinflammationBackground Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis. Method In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope. Results We showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states. Conclusion In all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.
Source: BioMedCentral - 🏆 22. / 71 Read more »