美国宾夕法尼亚大学Katalin Susztak和李铭尧小组近日取得一项新成果。他们对人类肾脏进行的单细胞多组学和空间分析表明，纤维化微环境与肾病进展有关。相关论文发表在2024年7月24日出版的《自然—遗传学》杂志上。

该研究团队生成了81个样本的高质量数据集，包括单细胞，单核，点水平(Visium)和单细胞分辨率(CosMx)空间RNA表达和单核开放染色质，捕获来自健康，糖尿病和高血压病变人肾脏的细胞。结合这些数据，研究人员识别细胞类型，并将它们映射到组织中的位置。空间数据的无偏差反卷积确定了以下不同的微环境:肾小球、免疫、小管和纤维化。

研究人员描述了健康和疾病中微环境的复杂组织，并发现纤维化微环境能够对人类肾脏进行分子分类，并且与传统的组织病理学相比，提供了更好的预后。该研究团队提供了人类肾脏和纤维化过程的全面的空间分解分子路线图，展示了空间转录组学的临床应用。

据了解，肾脏是人体中复杂的三维结构，然而肾脏健康和疾病的空间和分子原理仍然没有得到充分的了解。

附：英文原文

Title: Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression

Author: Abedini, Amin, Levinsohn, Jonathan, Kltzer, Konstantin A., Dumoulin, Bernhard, Ma, Ziyuan, Frederick, Julia, Dhillon, Poonam, Balzer, Michael S., Shrestha, Rojesh, Liu, Hongbo, Vitale, Steven, Bergeson, Andi M., Devalaraja-Narashimha, Kishor, Grandi, Paola, Bhattacharyya, Tanmoy, Hu, Erding, Pullen, Steven S., Boustany-Kari, Carine M., Guarnieri, Paolo, Karihaloo, Anil, Traum, Daniel, Yan, Hanying, Coleman, Kyle, Palmer, Matthew, Sarov-Blat, Lea, Morton, Lori, Hunter, Christopher A., Kaestner, Klaus H., Li, Mingyao, Susztak, Katalin

Issue&Volume: 2024-07-24

Abstract: Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue. Unbiased deconvolution of the spatial data identifies the following four distinct microenvironments: glomerular, immune, tubule and fibrotic. We describe the complex organization of microenvironments in health and disease and find that the fibrotic microenvironment is able to molecularly classify human kidneys and offers an improved prognosis compared to traditional histopathology. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.

DOI: 10.1038/s41588-024-01802-x

Source: https://www.nature.com/articles/s41588-024-01802-x