Project description:The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show neural tube defects (NTD). Here, we studied the transcriptomic profile of mouse embryos lacking SR-B1 to identify the molecular determinants of this phenotypic difference. We used RNA-Seq to analyze the expression of mRNA globally in E9.5 wild-type embryos and embryos lacking SR-B1 with or without NTD, in order to compare expression profiles in those groups and to identify putative genes driving phenotypic differences.
Project description:Innate-like B cells produce natural antibodies, and include marginal-zone (MZ) B cells and B1 cells. B1 cells have been well-studied in mice where they are pre-natally seeded into serous cavities, and are an important source of regulatory cytokines. A recent cell atlas study described putative ‘B1’ cells in human prenatal organs, but whether these cells persist in adult humans is unclear. Here, we identified ‘B1-like’ cells in the IgM+/IgA+ memory compartment in multiple human organs including kidney, lung and spleen. These cells were transcriptionally similar to murine B1 cells and human prenatal ‘B1’ cells, but distinct from MZ B cells. These adult human ‘B1-like’ cells expressed several canonical murine B1 cell markers, including AHNAK and BHLHE41. B-cell receptor (BCR) sequencing of paired human kidney and spleen samples showed IgM/IgA clones among adult kidney BCRs with a lower diversity and mutation rate than splenic cells, suggesting seeding independent of splenic B cells. Functionally, adult ‘B1-like’ cells expressed the regulatory cytokine TGF-beta, and had the highest number of inferred interactions with tissue myeloid cells, with macrophages in turn expressing B cell pro-survival cytokines. Altogether, our study provides evidence of ‘B1-like’ cells in homeostatic adult human organs.
Project description:Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation and the induction of arginine biosynthesis. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro, whereas LC/MS analysis demonstrated that the concentration of arginine was higher following VB1 supplementation. It is suggested that VB1 could be used for the treatment of tuberculosis potentially.
Project description:Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing and LC/MS. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation. LC/MS indicated that most of amino acids and ADP decreased in VB1 processed culture. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro. This study will be benefit for our deeply understanding for impact of VB1 to M.tuberculosis.
Project description:Identified a series of miRNAs transcriptionally regulated by vitamin D treatment within osteoblasts. Several miRNAs were validated in dose escalation experiments. Furthermore, downstream miRNA targets were appraised and found to regulate target message and protein levels. These findings were assessed in early and late passaged osteoblasts and found an age-dependent regulation of some miRNAs, while others were considered constituitiously expressed. Inhibitor studies of one key bone-related miRNA demonstrated the importance of this miRNA to regulate vitamin D-mediate osteoblastic differentiation during mineralizaition.