哥伦比亚大学Kam W. Leong课题组在研究中取得进展。他们提出了Squidiff：使用扩散模型预测细胞发育和对扰动的反应。2025年11月3日，国际知名学术期刊《自然—方法学》发表了这一成果。

在这里，该课题组人员提出了Squidiff，一个基于扩散模型的生成框架，预测不同细胞类型在响应环境变化时的转录组变化。研究小组证明了乌贼在细胞分化、基因扰动和药物反应预测方面的稳定性。通过持续的去噪和语义特征整合，Squidiff学习瞬时细胞状态，并预测随时间和条件的高分辨率转录组景观。

此外，研究人员应用Squidiff模拟血管类器官发育和细胞对中子辐照和生长因子的反应。他们的研究结果表明，Squidiff能够在计算机上筛选分子景观和细胞状态转变，促进快速的假设生成，并为细胞命运决定的调节原则提供有价值的见解。

据悉，单细胞测序彻底改变了他们对细胞异质性和对环境刺激的反应的理解。然而，绘制不同细胞类型的转录组变化以响应各种刺激并阐明潜在的疾病机制仍然具有挑战性。

附：英文原文

Title: Squidiff: predicting cellular development and responses to perturbations using a diffusion model

Author: He, Siyu, Zhu, Yuefei, Tavakol, Daniel Naveed, Ye, Haotian, Lao, Yeh-Hsing, Zhu, Zixian, Xu, Cong, Chauhan, Shradha, Garty, Guy, Tomer, Raju, Vunjak-Novakovic, Gordana, Zou, James, Azizi, Elham, Leong, Kam W.

Issue&Volume: 2025-11-03

Abstract: Single-cell sequencing has revolutionized our understanding of cellular heterogeneity and responses to environmental stimuli. However, mapping transcriptomic changes across diverse cell types in response to various stimuli and elucidating underlying disease mechanisms remains challenging. Here we present Squidiff, a diffusion model-based generative framework that predicts transcriptomic changes across diverse cell types in response to environmental changes. We demonstrate the robustness of Squidiff across cell differentiation, gene perturbation and drug response prediction. Through continuous denoising and semantic feature integration, Squidiff learns transient cell states and predicts high-resolution transcriptomic landscapes over time and conditions. Furthermore, we applied Squidiff to model blood vessel organoid development and cellular responses to neutron irradiation and growth factors. Our results demonstrate that Squidiff enables in silico screening of molecular landscapes and cellular state transitions, facilitating rapid hypothesis generation and providing valuable insights into the regulatory principles of cell fate decisions.

DOI: 10.1038/s41592-025-02877-y

Source: https://www.nature.com/articles/s41592-025-02877-y