生物
染色质
表观遗传学
单核苷酸多态性
表达数量性状基因座
遗传学
数量性状位点
染色体构象捕获
基因座(遗传学)
人口
基因
转录组
转录因子
基因表达
增强子
基因型
人口学
社会学
作者
Zhaowei Teng,Yun Zhu,Dazhen Lin,Qinggang Hao,Qiaoning Yue,Xiaochao Yu,Shuo Sun,Lihong Jiang,Sheng Lü
标识
DOI:10.1016/j.jgg.2023.01.009
摘要
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 high-throughput chromosome conformation capture. The structure analyses reveal 17.5% common and 28.5%-30% specific loops among BMMSCs, osteoblasts, and adipocytes. The subsequent correlation of genome-wide association studies and expression quantitative trait locus (eQTL) 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 291 SNPs are identified to affect the eQTL. 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI