Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.
Nat Commun. 2021 Apr 13;12(1):2190. doi: 10.1038/s41467-021-22368-w.
The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
单细胞转录组和染色质可及性数据集的整合使我们能够更深入地了解细胞异质性。我们进行了单核 ATAC（snATAC-seq）和 RNA（snRNA-seq）测序，生成了配对的、细胞类型特异性的染色质可及性和成人肾脏转录谱。我们证明 snATAC-seq 在细胞身份的分配上与 snRNA-seq 相当，并且可以进一步深入了解肾单位中的功能异质性。大多数差异可及的染色质区域定位于启动子，并且很大一部分与差异表达基因密切相关。转录因子结合基序的细胞类型特异性富集暗示 NF-κB 的激活，促进 VCAM1 的表达，并驱动近端肾小管上皮细胞亚群之间的转变。我们的多组学方法提高了在肾脏中检测独特细胞状态的能力，并重新定义了近端肾小管和升支粗段中的细胞异质性。
