Pan Yu, Liu Tao, Li Linfeng, He Liang, Pan Shu, Liu Yuwei
Department of Orthopedic Surgery, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.
School of Medicine, Jiangsu University, Zhenjiang 2012013, China.
Genes (Basel). 2024 Dec 4;15(12):1568. doi: 10.3390/genes15121568.
BACKGROUND/OBJECTIVES: Mesenchymal stem cells (MSCs) possess the remarkable ability to differentiate into various cell types, including osteoblasts. Understanding the molecular mechanisms governing MSC osteogenic differentiation is crucial for advancing clinical applications and our comprehension of complex disease processes. However, the key biological molecules regulating this process remain incompletely understood.
In this study, we conducted systematic re-analyses of published high-throughput transcriptomic datasets to identify and validate key biological molecules that dynamically regulate MSC osteogenic differentiation. Our approach involved a comprehensive analysis of gene expression patterns across human tissues, followed by the rigorous experimental validation of the identified candidates.
Through integrated analytical and experimental approaches, we utilized high-throughput transcriptomics to identify four critical regulators of MSC osteogenic differentiation: , , , and . Among these, and functioned as positive regulators, while and acted as negative regulators in osteogenesis. The regulatory roles of these genes in osteogenesis were further validated via overexpression experiments.
Our findings advance our understanding of MSC differentiation fate determination and open new therapeutic possibilities for bone-related disorders. The identification of these regulators provides a foundation for developing targeted interventions in regenerative medicine.
背景/目的:间充质干细胞(MSCs)具有分化为多种细胞类型(包括成骨细胞)的显著能力。了解调控MSCs成骨分化的分子机制对于推进临床应用以及我们对复杂疾病过程的理解至关重要。然而,调控这一过程的关键生物分子仍未完全明确。
在本研究中,我们对已发表的高通量转录组数据集进行了系统的重新分析,以识别和验证动态调控MSCs成骨分化的关键生物分子。我们的方法包括对人类组织中基因表达模式的全面分析,随后对鉴定出的候选分子进行严格的实验验证。
通过综合分析和实验方法,我们利用高通量转录组学鉴定出了MSCs成骨分化的四个关键调节因子: 、 、 和 。其中, 和 作为成骨的正调节因子,而 和 在成骨过程中起负调节作用。这些基因在成骨中的调节作用通过过表达实验得到进一步验证。
我们的研究结果增进了我们对MSCs分化命运决定的理解,并为骨相关疾病开辟了新的治疗可能性。这些调节因子的鉴定为再生医学中开发靶向干预措施提供了基础。