Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney.
Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney.
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DOI：
10.1038/s41467-021-22368-w
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发表时间：
2021-04-13
影响因子：
16.6
通讯作者：
Humphreys BD
中科院分区：
文献类型：
--
作者：
Muto Y;Wilson PC;Ledru N;Wu H;Dimke H;Waikar SS;Humphreys BD
单细胞转录组和染色质可及性数据集的整合使人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，以生成成对的、细胞类型特异性的染色质可及性和成人肾脏的转录谱。我们证明snATAC-seq在细胞身份分配方面与snRNA-seq相当，并且可以进一步完善我们对肾单位功能异质性的理解。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的基因密切相关。转录因子结合基序的细胞类型特异性富集暗示了NF-κB的激活，其促进VCAM 1表达并驱动近端小管上皮细胞亚群之间的转换。我们的多组学方法提高了检测肾脏内独特细胞状态的能力，并重新定义了近端小管和粗升支中的细胞异质性。人类肾脏的单细胞转录组和表观基因组测序突出了不同的细胞类型和状态。这些发现有助于表征一种新的受损近曲小管细胞群体，并说明了多组学方法表征人体组织的能力。
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. Single cell transcriptomic and epigenomic sequencing of human kidney highlight diverse cell types and states. These findings help characterize a novel population of injured proximal tubule cells and illustrate the power of multi-omic approaches to characterizing human tissue.
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影响因子：
5.2
作者：
Angelotti, Maria Lucia;Ronconi, Elisa;Romagnani, Paola
通讯作者：
Romagnani, Paola
早期和晚期糖尿病肾病肾脏转录组图谱的比较揭示了疾病进展的潜在新机制
影响因子：
7.7
作者：
Fan, Ying;Yi, Zhengzi;Wang, Niansong
通讯作者：
Wang, Niansong
影响因子：
4.6
作者：
Chambers, Brooke E.;Gerlach, Gary F.;Wingert, Rebecca A.
通讯作者：
Wingert, Rebecca A.
影响因子：
8.2
作者：
Ghezzi C;Loo DDF;Wright EM
通讯作者：
Wright EM
DOI：
10.1126/science.aau0730
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cao J;Cusanovich DA;Ramani V;Aghamirzaie D;Pliner HA;Hill AJ;Daza RM;McFaline-Figueroa JL;Packer JS;Christiansen L;Steemers FJ;Adey AC;Trapnell C;Shendure J
通讯作者：
Shendure J