撰文丨王聪 编辑丨王多鱼 排版丨水成文 类器官 （ Organoid ） 是从干细胞衍生出的三维 （3D） 结构，能够重现相应组织的关键结构和功能特 征。与传统的二维 （2D） 细胞系相比，人类类器官能提供更贴近人体生理的实验模型。它们能够捕捉人 体组织的复杂性和异质性，从而有助于研究疾病机制、药物疗效和毒性。当由患者来源的生成时，类器官 还能用于评估个体对治疗药物的响应。 近日，"类器官之父" Hans Clevers 教授、 王代松 博士等在 Nature 旗下综述期刊 Nature Reviews Drug Discovery 上发表了题为 ： Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges 的研究论文。 在这篇综述中，作者们探讨了 类器官在药物发现中的应用 ，概述了当前的生成和维持类器官的方法，考察 了它们在疾病建模、药物筛选和安全性评估方面的应用，并考虑了监管方面以及在药物发现中更广泛采用 所面临的挑战。 在药物研发领域，体外模型发挥着关键作用，为研究细胞对药物的反应提 ...

Summary of the Conference Call for 诺禾致源 (Nuohe Zhiyuan) Company Overview - **Company**: 诺禾致源 (Nuohe Zhiyuan) - **Period**: January to September 2025 Key Financial Metrics - **Total Revenue**: 15.81 billion CNY, up 4.05% year-on-year [2][3] - **Q3 Revenue**: 5.41 billion CNY, up 3.47% year-on-year [3] - **Overseas Revenue**: 7.92 billion CNY, up 4.1% year-on-year, accounting for 50.09% of total revenue [2][3] - **Q3 Overseas Revenue**: 2.58 billion CNY, down 0.48% year-on-year [3] - **Domestic Revenue**: 7.89 billion CNY, up 4% year-on-year [2] - **Q3 Domestic Revenue**: 2.82 billion CNY, up 7.37% year-on-year, and up 8.61% quarter-on-quarter [5] - **Gross Margin**: 41.9%, down 0.7 percentage points year-on-year [10] - **Net Profit**: 1.16 billion CNY, down 10.17% year-on-year, with a net profit margin of 7.31% [11] - **R&D Investment**: 56.1 million CNY in Q3, focusing on emerging fields [12] Revenue Breakdown by Market - **Americas**: Q3 revenue down 12% due to changes in research funding and policy impacts [4] - **EMEA**: Q3 revenue down 12%, affected by project completion and funding transitions [4] - **Europe**: Q3 revenue up 19%, indicating strong performance [4] - **Customer Segmentation**: 70% of revenue from universities and research institutions, 30% from hospitals and enterprises [6] Product and Service Performance - **Life Sciences Research Services**: Revenue of 5.52 billion CNY, up 6.21% year-on-year [7] - **Monitoring and Sequencing Platform Services**: Revenue of 7.7 billion CNY, up 3.23% year-on-year, but Q3 revenue down 3.42% [7] - **Emerging Business Contributions**: Approximately 32% of total revenue, up 4 percentage points year-on-year, with a growth of about 20% [8] R&D and Innovation - **R&D Focus Areas**: Single-cell genomics, spatial genomics, proteomics, metabolomics, epigenetics, and long-read sequencing [12][18] - **AI Integration**: Progress in AI applications, particularly in omics data analysis and virtual cell modeling [20][28] Market Challenges and Strategies - **Domestic Market Competition**: Increased competition leading to a 30% price drop; company aims to reduce competition through mergers and acquisitions [16][23] - **Geopolitical Impact**: U.S. market affected by geopolitical tensions, but the company maintains strong relationships in key regions [21] - **Cash Flow Management**: Operating cash flow was negative 87 million CNY for the first nine months, but turned positive in Q3 at 77 million CNY [14] Future Outlook - **Expansion Plans**: Continued investment in overseas markets, including new laboratories in Singapore and Europe [30] - **Focus on NGS and AI**: Anticipated growth in NGS applications and AI integration to enhance research capabilities [24][28] Additional Insights - **Customer Base Growth**: Stable customer structure with a slight increase in contributions from universities and research institutions [6] - **Cash Flow Volatility**: Short-term fluctuations in cash flow due to proactive risk management strategies [14] - **Regulatory Environment**: Ongoing adjustments to align with changing policies in the domestic and international markets [26][27]

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].