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- 저자 : unescu, Teodor G. (검색결과 1 건)
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Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq
Chen, Lihe,Lee, Jae Wook,Chou, Chung-Lin,Nair, Anil V.,Battistone, Maria A.,Pă,unescu, Teodor G.,Merkulova, Maria,Breton, Sylvie,Verlander, Jill W.,Wall, Susan M.,Brown, Dennis,Burg, Maurice B. National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.46
<P><B>Significance</B></P><P>A long-term goal in mammalian biology is to identify the genes expressed in every cell type of the body. In the kidney, the expressed genes (i.e., transcriptome) of all epithelial cell types have already been identified with the exception of the cells that make up the renal collecting duct, which is responsible for regulation of blood pressure and body fluid composition. Here, single-cell RNA-sequencing was used in mouse to identify transcriptomes for the major collecting duct cell types: type A intercalated cells, type B intercalated cells, and principal cells. The information was used to create a publicly accessible online resource. The data allowed identification of genes that are selectively expressed in each cell type, which is informative for cell-level understanding of physiology and pathophysiology.</P><P>Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit. Single-cell RNA-seq using the IC- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs, and PCs. The data were used to create a freely accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters, and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing aquaporin-2 and anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., <I>Notch2</I> chiefly in PCs vs. <I>Jag1</I> chiefly in ICs), suggesting signaling cross-talk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.</P>
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