跨物种单细胞肾图谱中个体患者通路协调分析，这一成果由宾夕法尼亚大学Katalin Susztak团队经过不懈努力而取得。相关论文于2025年8月7日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

在这里，该研究团队创建了一个集成的单细胞肾脏图谱，包括来自140个样本的100多万个细胞，在人类和啮齿动物模型中定义了70多种保守的细胞状态。该课题组开发了CellSpectra，这是一种量化细胞功能中基因表达协调变化的计算工具，该课题组将其应用于肾脏和肺癌的数据。该工具为他们的患者水平单细胞功能分析报告提供了动力，该报告强调了个体中通路基因表达协调中细胞类型特异性变化。他们的跨物种图谱促进了啮齿动物模型的选择，该模型密切反映了在患者样本中观察到的细胞和途径水平特征，促进了单细胞方法在临床精准医学中的应用。最后，以实验模型为主题，该课题组研究人员展示了他们的信息学方法如何应用于合适治疗方法的潜在选择。

据介绍，单细胞RNA测序在临床和转化研究中的主题受到个体患者和跨物种差异中识别细胞类型特异性，靶向分子变化的挑战的限制。

附：英文原文

Title: Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas

Author: Kltzer, Konstantin A., Abedini, Amin, Li, Shen, Balzer, Michael S., Liang, Xiujie, Levinsohn, Jonathan, Ha, Eunji, Dumoulin, Bernhard, Hogan, Jonathan J., Quinn, Ghazal, Bloom, Roy D., Schuller, Max, Eller, Kathrin, Halmos, Balazs, Zhang, Nancy R., Susztak, Katalin

Issue&Volume: 2025-08-07

Abstract: The use of single-cell RNA sequencing in clinical and translational research is limited by the challenge of identifying cell-type-specific, targetable molecular changes in individual patients and cross-species differences. Here we created an integrated single-cell kidney atlas including over 1 million cells from 140 samples, defining more than 70 conserved cell states in human and rodent models. We developed CellSpectra, a computational tool that quantifies changes in gene expression coordination across cellular functions, which we applied to kidney and lung cancer data. This tool powers our patient-level single-cell functional profiling report, which highlights cell-type-specific changes in the coordination of pathway gene expression in individuals. Our cross-species atlas facilitates the selection of a rodent model that closely reflects the cellular and pathway-level signatures observed in patient samples, advancing the application of single-cell methodologies in clinical precision medicine. Finally, using experimental models, we demonstrate how our informatics approach can be applied for the potential selection of suitable therapeutics.

DOI: 10.1038/s41588-025-02285-0

Source: https://www.nature.com/articles/s41588-025-02285-0