Mouse Anti Human Fbln2 Hybridoma [DQUD-Gcmo3-3E0]

Many genes are associated with the differentiation of neural stem cells (NSCs) into astrocytes, the most abundant and functionally diverse population of glial cells in the central nervous system, particularly in the brain. In the present study, we differentiated NSCs from the forebrain of embryonic day 14.5 mouse embryos into astrocytes over 1 and 7 days. We identified transcriptomes of NSCs and astrocytes using RNA sequencing and analyzed enriched gene networks, signal pathways, and ontology. To identify important regulators of differentiation, we performed gene clustering according to expression patterns and promoter CG types. Our data show that genes related to system development, including Fbln2, Bcan, Ncam1, Itih3, Tnr, and Vcan, regulate NSC differentiation through WNT/beta-catenin and epithelial to mesenchymal transition pathways. We identified many CG-rich promoter genes related to basic cellular maintenance such as transcription, translation, and structural components and CG-poor promoter genes that are highly associated with cell-type-specific functions or play important roles during development. Our study provides a foundation for further research on NSC differentiation and the future application of stem cells.

OBJECTIVES: Serrated polyposis syndrome (SPS) is a complex disorder with a high risk of colorectal cancer for which the germline factors remain largely unknown. Here, we combined whole-exome sequencing (WES) and linkage studies in families with multiple members affected by SPS to identify candidate genes harboring rare variants with higher penetrance effects. METHODS: Thirty-nine affected subjects from 16 extended SPS families underwent WES. Genome-wide linkage analysis was performed under linear and exponential models. The contribution of rare coding variants selected to be highly pathogenic was assessed using the gene-based segregation test. RESULTS: significant linkage peak was identified on chromosome 3p25.2-p22.3 (maxSNP = rs2293787; LODlinear = 2.311, LODexp = 2.11), which logarithm of the odds (LOD) score increased after fine mapping for the same marker (maxSNP = rs2293787; LODlinear = 2.4, LODexp = 2.25). This linkage signal was replicated in 10 independent sets of random markers from this locus. To assess the contribution of rare variants predicted to be pathogenic, we performed a family-based segregation test with 11 rare variants predicted to be deleterious from 10 genes under the linkage intervals. This analysis showed significant segregation of rare variants with SPS in CAPT7, TMEM43, NGLY1, and FBLN2 genes (weighted Pvalue > 0.007). DISCUSSION: Protein network analysis suggested FBLN2 as the most plausible candidate genes for germline SPS predisposition. Etiologic rare variants implicated in disease predisposition may be identified by combining traditional linkage with WES data. This powerful approach was effective for the identification of a new candidate gene for hereditary SPS.