{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:11:16Z","timestamp":1790835076488,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["ZIA-HL001285"],"award-info":[{"award-number":["ZIA-HL001285"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["ZIA-HL006129"],"award-info":[{"award-number":["ZIA-HL006129"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["2020 Bench-to-Bedside Award"],"award-info":[{"award-number":["2020 Bench-to-Bedside Award"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,4]]},"abstract":"\n Significance Statement<\/jats:title>\n \n There are at least 14 different renal tubule segments, each with characteristic cell types with distinct functions. Although the advent of RNA sequencing (RNA-seq) has greatly improved our understanding of gene expression in these renal epithelial cell types, detailed mapping of transcripts has been limited by methods that tend to be biased toward transcript ends. Coupling full-length RNA-seq analysis with renal tubule microdissection characterized gene expression along the mouse renal tubule, including mapping of transcript abundance and alternative exon usage. The data provide a comprehensive view of gene expression along the nephron and collecting duct, made available to scientists\n via<\/jats:italic>\n a user-friendly web resource.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n The repertoire of protein expression along the renal tubule depends both on regulation of transcription and regulation of alternative splicing that can generate multiple proteins from a single gene.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A full-length, small-sample RNA-seq protocol profiled transcriptomes for all 14 renal tubule segments microdissected from mouse kidneys.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This study identified >34,000 transcripts, including 3709 that were expressed in a segment-specific manner. All data are provided as an online resource (https:\/\/esbl.nhlbi.nih.gov\/MRECA\/Nephron\/). Many of the genes expressed in unique patterns along the renal tubule were solute carriers, transcription factors, or G protein\u2013coupled receptors that account for segment-specific function. Mapping the distribution of transcripts associated with Wnk-SPAK-PKA signaling, renin-angiotensin-aldosterone signaling, and cystic diseases of the kidney illustrated the applications of the online resource. The method allowed full-length mapping of RNA-seq reads, which facilitated comprehensive, unbiased characterization of alternative exon usage along the renal tubule, including known isoforms of\n Cldn10<\/jats:italic>\n ,\n Kcnj1<\/jats:italic>\n (ROMK),\n Slc12a1<\/jats:italic>\n (NKCC2),\n Wnk1<\/jats:italic>\n ,\n Stk39<\/jats:italic>\n (SPAK), and\n Slc14a2<\/jats:italic>\n (UT-A urea transporter). It also identified many novel isoforms with segment-specific distribution. These included variants associated with altered protein structure (\n Slc9a8<\/jats:italic>\n ,\n Khk<\/jats:italic>\n ,\n Tsc22d1<\/jats:italic>\n , and\n Scoc<\/jats:italic>\n ), and variants that may affect untranslated, regulatory regions of transcripts (\n Pth1r<\/jats:italic>\n ,\n Pkar1a<\/jats:italic>\n , and\n Dab2<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Full-length, unbiased sequencing of transcripts identified gene-expression patterns along the mouse renal tubule. The data, provided as an online resource, include both quantitative and qualitative differences in transcripts. Identification of alternative splicing along the renal tubule may prove critical to understanding renal physiology and pathophysiology.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020101406","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T14:31:33Z","timestamp":1614954693000},"page":"897-912","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":215,"title":["A Comprehensive Map of mRNAs and Their Isoforms across All 14 Renal Tubule Segments of Mouse"],"prefix":"10.1681","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-6364","authenticated-orcid":false,"given":"Lihe","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Lin","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2276-8091","authenticated-orcid":false,"given":"Mark A.","family":"Knepper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","year":"2012","journal-title":"Nature"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"B3-20240826","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1681\/ASN.2014111067","article-title":"Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes","volume":"26","author":"Lee","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B4-20240826","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.molcel.2018.10.020","article-title":"Comparative analysis of droplet-based ultra-high-throughput single-cell RNA-seq systems","volume":"73","author":"Zhang","year":"2019","journal-title":"Mol Cell"},{"key":"B5-20240826","doi-asserted-by":"crossref","first-page":"E9989","DOI":"10.1073\/pnas.1710964114","article-title":"Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq","volume":"114","author":"Chen","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B6-20240826","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B7-20240826","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13059-016-0924-1","article-title":"JBrowse: A dynamic web platform for genome visualization and analysis","volume":"17","author":"Buels","year":"2016","journal-title":"Genome Biol"},{"key":"B8-20240826","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: Accurate transcript quantification from RNA-seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"B9-20240826","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B10-20240826","doi-asserted-by":"crossref","first-page":"e11752","DOI":"10.7554\/eLife.11752","article-title":"A new view of transcriptome complexity and regulation through the lens of local splicing variations","volume":"5","author":"Vaquero-Garcia","year":"2016","journal-title":"eLife"},{"key":"B11-20240826","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.devcel.2019.10.005","article-title":"Single-cell profiling reveals sex, lineage, and regional diversity in the mouse kidney","volume":"51","author":"Ransick","year":"2019","journal-title":"Dev Cell"},{"key":"B12-20240826","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ki.1988.1","article-title":"A standard nomenclature for structures of the kidney. 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