Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways
应用于狼疮性肾炎的管状细胞和角质形成细胞单细胞转录组学揭示了I型IFN和纤维化相关通路
摘要：
The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFNresponse signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.
导致肾损伤和狼疮性肾炎（LN）异质性的分子和细胞过程尚不清楚。我们将单细胞RNA测序（scRNA-seq）应用于来自LN患者的肾活组织检查，并评估皮肤活检作为肾病的诊断和预后标志物的潜在来源。管状细胞和角质形成细胞中的I型干扰素（IFN） - 反应特征区分LN患者与健康对照受试者。此外，管状细胞中的高IFN应答特征和纤维化特征各自与对治疗无反应相关。来自患有增生性，膜性和混合性LN的患者的肾小管细胞的分析表明与炎症和纤维化相关的途径，其提供对其组织学差异的洞察。总之，我们将scRNA-seq应用于LN以解构其异质性并确定用于个性化治疗方法的新靶标。