骨质疏松（OP）是骨代谢失衡相关的全身性退行性骨病，严重威胁人类身心健康，发病机制未明。骨髓间充质干细胞（BMMSC）是成骨细胞和脂肪细胞的前体干细胞，其成骨成脂分化方向决定了骨形成与骨吸收的平衡，进而影响骨质疏松的发生发展。染色质三维空间构象改变在BMMSC不同分化方向中发挥重要作用，在基因序列未发生改变的情况下，线性距离较远的启动子和增强子相互作用发生改变，继而导致下游基因调控发生改变，从而引起基因表达产生差异。在前期工作中，本课题组开发出一种简单、低成本、低噪音的全基因组染色质构象捕获技术（DLO Hi-C）。本项目拟采用该新型DLO Hi-C技术构建BMMSC及分化后的成骨细胞、脂肪细胞测序文库，以高通量测序技术和生信分析技术为基础，深入探究染色质三维构象对BMMSC成骨成脂分化影响的分子机制，解析与BMMSC分化相关的基因与转录调控元件，进而为揭示骨质疏松的发生发展奠定理论基础。

Osteoporosis is a systemic degenerative bone disease related to the imbalance of bone metabolism, which poses a serious threat to human physical and mental health, and its pathogenesis remains unclear. Bone marrow mesenchymal stem cells (BMMSC) are the progenitor stem cells of osteoblasts and adipocytes. The direction of osteogenic and lipogenic differentiation determines the balance of bone formation and absorption, thus affecting the occurrence and development of osteoporosis. The three-dimensional conformation changes of chromatin play an important role in the different differentiation directions of BMMSC. When the gene sequence is not changed, the interaction between promoters and enhancers with a relatively farther linear distance is changed, which in turn leads to changes in the regulation of downstream gene , thereby causing differences in gene expression. In the preliminary work, our group developed a simple, cost-effective, low-noise technology, DLO Hi-C, for whole-genome chromatin conformation capture. This project intends to use the new DLO Hi-C technology to construct BMMSC and differentiated cell sequencing library. Based on high-throughput sequencing technology and bio-information analysis technology, this study will further explore the molecular mechanism of the influence of chromatin three-dimensional conformation on the differentiation direction of BMMSC, analyze the genes and transcriptional regulatory elements related to BMMSC differentiation, and thus lay a theoretical foundation for revealing the occurrence and development of osteoporosis.