Deciphering the chromatin spatial organization landscapes during BMMSC differentiation  

作　　者：Zhaowei Teng Yun Zhu Da Lin Qinggang Hao Qiaoning Yue Xiaochao Yu Shuo Sun Lihong Jiang Sheng Lu 

机构地区：[1]Department of Orthopedics,The First People's Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology,Kunming,Yunnan 650032,China [2]Key Laboratory of Yunnan Provincial Innovative Application of Traditional Chinese Medicine,The First People's Hospital of Yunnan Province,Kunming,Yunnan 650032,China [3]Clinical Medical Research Center,The First People's Hospital of Yunnan Province,Kunming,Yunnan 650032,China [4]The Sixth Affiliated Hospital of Kunming Medical University,Yuxi,Yunnan 653100,China [5]State Key Laboratory of Agricultural Microbiology,Huazhong Agricultural University,Wuhan,Hubei 430070,China [6]Center for Life Sciences,School of Life Sciences,Yunnan University,Kunming,Yunnan 650504,China

出　　处：《Journal of Genetics and Genomics》2023年第4期264-275,共12页遗传学报（英文版）

基　　金：supported in part by the National Natural Science Foundation of China,grant no.31960136;the Yunnan health training project for high-level talents;Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine,grant no.202105AG070032;Kunming University of Science and Technology&the First People’s Hospital of Yunnan Province Joint Special Project on Medical Research,grant no.KUSTKH2022002Z;2021 Center of Yunnan Orthopedics and Sports Rehabilitation Clinical Medical Research,grant no.2022YJZXGK04;the 2023 Project of Yunnan Basic Research,grant no.202201AT070079 and 202201AT070285。

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 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.

关 键 词：Bone marrow mesenchymal stem cells DIFFERENTIATION Hi-C ATAC-Seq Single nucleotide polymorphisms Genome-wide association studies 

分 类 号：Q343[生物学—遗传学]