PMID- 21888672 OWN - NLM STAT- MEDLINE VI - 12 TI - Refining transcriptional programs in kidney development by integration of deep RNA-sequencing and array-based spatial profiling. PG - 441 LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Bmc Genomics JT - BMC genomics JID - 100965258 IS - 1471-2164 (Electronic) LID - 10.1186/1471-2164-12-441 [doi] FAU - Thiagarajan, Rathi D AU - Thiagarajan RD AD - Institute for Molecular Bioscience, The University of Queensland, St, Lucia QLD 4072, Australia. rathi@scripps.edu FAU - Cloonan, Nicole AU - Cloonan N FAU - Gardiner, Brooke B AU - Gardiner BB FAU - Mercer, Tim R AU - Mercer TR FAU - Kolle, Gabriel AU - Kolle G FAU - Nourbakhsh, Ehsan AU - Nourbakhsh E FAU - Wani, Shivangi AU - Wani S FAU - Tang, Dave AU - Tang D FAU - Krishnan, Keerthana AU - Krishnan K FAU - Georgas, Kylie M AU - Georgas KM FAU - Rumballe, Bree A AU - Rumballe BA FAU - Chiu, Han S AU - Chiu HS FAU - Steen, Jason A AU - Steen JA FAU - Mattick, John S AU - Mattick JS FAU - Little, Melissa H AU - Little MH FAU - Grimmond, Sean M AU - Grimmond SM IS - 1471-2164 (Linking) RN - 0 (MicroRNAs) RN - 0 (RNA, Antisense) RN - 0 (RNA, Messenger) SB - IM MH - Alternative Splicing MH - Animals MH - Exons MH - High-Throughput Nucleotide Sequencing/methods MH - Kidney/embryology/*metabolism MH - Mice MH - MicroRNAs/*genetics MH - Organogenesis MH - RNA, Antisense/genetics MH - RNA, Messenger/*genetics MH - Sequence Analysis, RNA/*methods MH - Transcription, Genetic MH - *Transcriptome PMC - PMC3180702 DCOM- 20120111 LR - 20211020 DP - 2011 Sep 05 DEP - 20110905 AB - BACKGROUND: The developing mouse kidney is currently the best-characterized model of organogenesis at a transcriptional level. Detailed spatial maps have been generated for gene expression profiling combined with systematic in situ screening. These studies, however, fall short of capturing the transcriptional complexity arising from each locus due to the limited scope of microarray-based technology, which is largely based on "gene-centric" models. RESULTS: To address this, the polyadenylated RNA and microRNA transcriptomes of the 15.5 dpc mouse kidney were profiled using strand-specific RNA-sequencing (RNA-Seq) to a depth sufficient to complement spatial maps from pre-existing microarray datasets. The transcriptional complexity of RNAs arising from mouse RefSeq loci was catalogued; including 3568 alternatively spliced transcripts and 532 uncharacterized alternate 3' UTRs. Antisense expressions for 60% of RefSeq genes was also detected including uncharacterized non-coding transcripts overlapping kidney progenitor markers, Six2 and Sall1, and were validated by section in situ hybridization. Analysis of genes known to be involved in kidney development, particularly during mesenchymal-to-epithelial transition, showed an enrichment of non-coding antisense transcripts extended along protein-coding RNAs. CONCLUSION: The resulting resource further refines the transcriptomic cartography of kidney organogenesis by integrating deep RNA sequencing data with locus-based information from previously published expression atlases. The added resolution of RNA-Seq has provided the basis for a transition from classical gene-centric models of kidney development towards more accurate and detailed "transcript-centric" representations, which highlights the extent of transcriptional complexity of genes that direct complex development events.