Project description:Dentin is a major mineralized component of teeth generated by odontoblasts. Several types of histone methylation have been reported to play important roles in odontoblast differentiation and dentinogenesis. However, the role of methylation on histone 3 at lysine 36 (H3K36) remains enigmatic. Here we find a high expression of SETD2, a methyltransferase catalyzing the trimethylation of H3K36 (H3K36me3), in the odontoblast layer. In vitro knockdown experiments and in vivo observations of two conditional knockout mouse models reveal SETD2 is essential for odontoblast differentiation and dentinogenesis. Integrated analyses of RNA sequencing and Spike-in Cleavage Under Targets and Tagmentation sequencing data show SETD2 is crucial for both H3K36me3 occupancy on the loci of Col11a2 and Sema3e and their transcription. Further experiments verify COL11A2 and SEMA3E act upstream of AKT1 signaling, promoting odontoblastic differentiation. In vitro and in vivo activation of AKT1 using SC79 (an AKT activator) partially rescues the impaired odontoblast differentiation caused by Setd2 knockdown or deficiency. Therefore, our findings indicate that H3K36me3 mediated by SETD2 is essential for dentinogenesis through regulating the expression of Col11a2 and Sema3e and AKT1 signaling.
2025-02-03 | GSE288311 | GEO
Project description:WES sequecning of AI family in China
| PRJNA1184796 | ENA
Project description:WES data for bilateral renal agenesis family
Project description:Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.12p12 duplication has not yet been reported. We first report the 11p11.12p12 duplication in a family with intellectual disability and craniofacial anomalies. 11p11.12p12 duplication syndrome was identified by karyotype analysis. Next-generation sequencing (NGS) analysis clarified the location of the chromosomal variations, which was confirmed by chromosome microarray analysis (CMA). Whole-exome sequencing (WES) was performed to exclude single nucleotide variations (SNVs). The raw data of NGS analysis and WES have been submitted to SRA, the accession number is PRJNA713823.
Project description:Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality. Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality. Current methods for detection of copy number aberrations (CNA) from whole-exome sequencing (WES) data are based on the read counts of the captured exons only. However, accurate CNA determination is complicated by the non-uniform read depth and uneven distribution of exons. Therefore, we developed ENCODER (ENhanced COpy number Detection from Exome Reads), which eludes these problems. By exploiting the ‘off-target’ sequence reads, it allows for creation of robust copy number profiles from WES. The accuracy of ENCODER compares to approaches specifically designed for copy number detection, and outperforms current exon-based WES methods, particularly in samples of low quality. DNA copy number profiles generated with a new tool, ENCODER, were compared to DNA copy number profiles from SNP6, NimbleGen and low-coverage Whole Genome Sequencing.