Project description:MicroRNAs are small non-coding RNAs that are critical in post-transcriptional regulation. According to the latest miRBase (v22), there are 617 annotated pre-miRNAs in Macaca mulatta, which is much less than 1917 in human, although both of these two species are primates. To improve the annotation of miRNAs in Macaca mulatta, we generated 12 small RNA profiles from 8 tissues and perform comprehensive analysis of these profiles. We identified 613 conserved pre-miRNAs that have not been reported in Macaca mulatta and 25 novel miRNAs. Furthermore, we identified 996 editing sites with significant editing levels from 250 pre-miRNAs after analyzing the 12 self-generated and 58 additional published sRNA-seq profiles from different types of organs or tissues. Our results show that the distribution of different miRNA editing types in Macaca mulatta is different from that in human brains. Particularly, there are much more small indel events in miRNAs of Macaca mulatta than in human brains. These results significantly increase our understanding of miRNAs and their editing events in Macaca mulatta.
Project description:Cytokine-independent detection of antigen-specific germinal center T follicular helper (Tfh) cells in immunized non-human primates using a live cell Activation Induced Marker (AIM) technique
Project description:Biomarker studies for early stage or preclinical hepatocellular carcinomas (HCC) are hindered by the difficulties of obtaining samples from asymptomatic individuals. We established animal models using irradiated mice to investigate circulating miRNA as non-invasive markers for detection of early stage HCC. We hypothesized that certain miRNAs that play pivotal roles in molecular pathways are conserved across species and identification of these miRNAs will facilitate studying human markers in mice. To test the hypothesis, we performed weighted gene co-expression analysis by integrating circulating miRNA and tumor gene expression profiles from individual mice and discovered hub miRNAs in highly correlated expression modules. We validated the hub miRNAs using F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders and identified 38 circulating miRNA markers associated with radiation-induced HCC. Through literacy search, we selected 10 human HCC-associated circulating miRNAs that had been validated in multiple independent patient cohorts. Nine of the 10 human markers overlapped with the mouse hub miRNAs, indicating the feasibility of using mouse model to study human circulating HCC markers. Using serially collected plasma samples from irradiated mice, we studied the kinetics of circulating miRNAs. We found that the mouse plasma levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching towards HCC detection, indicating the correlations of the 4 miRNAs with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started months before HCC detection, ranging from 17.5 to 6.8 months. Our data demonstrated that the 4 circulating miRNAs were sensitive biomarkers potentially valuable for the screening of early stage HCC.