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Deciphering the chromatin spatial organization landscapes during BMMSC differentiation 被引量:1
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作者 zhaowei teng Yun Zhu +6 位作者 Da Lin Qinggang Hao Qiaoning Yue Xiaochao Yu Shuo Sun Lihong Jiang Sheng Lu 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2023年第4期264-275,共12页
The differentiation imbalance in bone marrow mesenchymal stem cells(BMMSCs)is critical for the development of bone density diseases as the population ages.BMMSCs are precursor cells for osteoblasts and adipocytes;howe... The differentiation imbalance in bone marrow mesenchymal stem cells(BMMSCs)is critical for the development of bone density diseases as the population ages.BMMSCs are precursor cells for osteoblasts and adipocytes;however,the chromatin organization landscapes during BMMSC differentiation remain elusive.In this study,we systematically delineate the four-dimensional genome and dynamic epigenetic atlas of BMMSCs by RNA sequencing,assay for transposase-accessible chromatin sequencing,and highthroughput chromosome conformation capture.The structure analyses reveal 17.5%common and28.5%-30%specific loops among BMMSCs,osteoblasts,and adipocytes.The subsequent correlation of genome-wide association studies and expression quantitative trait locus(e QTL)data with multi-omics analysis reveal 274 genes and 3634 single nucleotide polymorphisms(SNPs)associated with bone degeneration and osteoporosis(OP).We hypothesize that SNP mutations affect transcription factor(TF)binding sites,thereby affecting changes in gene expression.Furthermore,26 motifs,260 TFs,and 291SNPs are identified to affect the e QTL.Among these genes,DAAM2,TIMP2,and TMEM241 are found to be essential for diseases such as bone degeneration and OP and may serve as potential drug targets. 展开更多
关键词 Bone marrow mesenchymal stem cells DIFFERENTIATION Hi-C ATAC-Seq Single nucleotide polymorphisms Genome-wide association studies
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