宾夕法尼亚大学Katalin Susztak小组在研究中取得进展。他们的论文发现了糖尿病肾病的空间图谱揭示了一个富含B细胞的亚群。这一研究成果发表在2026年4月29日出版的国际学术期刊《自然》上。

在这里，课题组人员将Xenium和CosMx单细胞空间转录组学与单核RNA测序相结合，构建一个跨平台的肾脏图谱，使组织结构可用于预后，非侵入性检测和患者选择。使用该图谱，研究团队定义了可复制的组织壁龛和损伤相关的微环境，并揭示了随着疾病扩大和肾功能恶化的纤维化背景。在这个结构中，课题组人员确定了一个以B细胞为主的三级淋巴结构样免疫微环境，它定义了一个独特的DKD亚群，加速了肾终点的进展。小组开发了组织生物标志物和匹配的血浆蛋白面板，以捕获这种生物学特性，在人群生物库中对患者进行分层，并改进临床模型之外的风险预测-支持它们在未来B细胞靶向DKD试验中生物标志物引导选择的潜力。

研究人员表示，糖尿病肾病（DKD）是肾衰竭的主要疾病，其特点是临床和分子异质性，使得治疗发展极其困难。

附：英文原文

Title: Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup

Author: Dumoulin, Bernhard, Levinsohn, Jonathan, Kltzer, Konstantin A., Li, Chenyu, Mao, Liran, Ha, Eunji, Mohandes, Samer, Nguyen, Thao, Paruzzo, Luca, Hirohama, Daigoro, Fang, Victoria, Bhoj, Vijay G., Parhiz, Hamideh, Andrade-Silva, Magaiver, Abedini, Amin, Bergeson, Andi, Traum, Daniel, May, Michael J., Kaestner, Klaus H., Ruella, Marco, McAllister, Fiona Elizabeth, Hakimi, A. Ari, Li, Mingyao, Palmer, Matthew, Wherry, E. John, Hunter, Christopher A., Cancro, Michael Paul, Susztak, Katalin

Issue&Volume: 2026-04-29

Abstract: Diabetic kidney disease (DKD), the leading cause of kidney failure, is marked by clinical and molecular heterogeneity, making therapeutic development exceedingly difficult1. Here we used Xenium and CosMx single-cell spatial transcriptomics, integrated with single-nucleus RNA sequencing, to build a cross-platform kidney atlas that makes tissue architecture computable for prognosis, non-invasive detection and patient selection. Using this atlas, we defined reproducible tissue niches and injury-linked microenvironments and uncovered a profibrotic context that expands with disease and tracks with worse kidney function. Within this architecture, we identified a B cell-predominant, tertiary lymphoid structure-like immune microenvironment that defines a distinct DKD subset with accelerated progression to renal end-points. We developed tissue biomarkers and a matched plasma protein panel that capture this biology, stratify patients in a population biobank and improve risk prediction beyond clinical models—supporting their potential for biomarker-guided selection in future B cell-targeted DKD trials.

DOI: 10.1038/s41586-026-10363-4

Source: https://www.nature.com/articles/s41586-026-10363-4