Nature Genetics：陈万泽团队开发单细胞转录因子测序技术，剖析转录因子剂量对细胞重编程异质性的影响

Core Viewpoint - The article discusses the development of scTF-seq technology, which enables dose-sensitive large-scale gene perturbation single-cell genomics, revealing complex, nonlinear effects of gene dosage on cell fate regulation [4][11]. Group 1: Technology Development - The scTF-seq technology was developed by a collaboration between the Shenzhen Institute of Advanced Technology and the Swiss Federal Institute of Technology in Lausanne, allowing for systematic analysis of gene dosage effects in cell reprogramming [4][16]. - This technology utilizes the inherent noise of the Tet-on promoter and differences in expression activity based on the integration sites of retroviral genomes, achieving a wide dosage distribution of transgenes [9]. Group 2: Gene Dosage Effects - The study found that gene dosage has complex, nonlinear effects on cell fate, exemplified by KLF4 driving different gene expression patterns related to bone formation, cell structure assembly, or epithelial development at varying doses [11]. - Gene dosage effects are closely linked to other cellular processes, such as the cell cycle, with specific genes like CEBPA and PPARG promoting cell cycle exit and fat differentiation at high doses [13]. Group 3: Multi-gene Interactions - In combinatorial perturbation experiments, the interactions between different transcription factors depend not only on the gene combinations but also significantly on gene dosage, exhibiting reversible synergistic or antagonistic effects [15]. - The research highlights that gene dosage shapes the interaction patterns between genes and cellular processes, as well as the cooperative and competitive relationships among multiple genes [15].