Refining transcriptional programs in kidney development by integration of deep RNA-sequencing and array-based spatial profiling.

BMC Genomics 2011 Sep 5;12:441. Epub 2011 Sep 5.

Institute for Molecular Bioscience, The University of Queensland, St, Lucia QLD 4072, Australia.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-12-441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180702PMC
September 2011
25 Reads

Publication Analysis

Top Keywords

kidney development
12
transcriptional complexity
12
mouse kidney
8
spatial maps
8
kidney
7
complexity rnas
4
rnas arising
4
arising mouse
4
data locus-based
4
microarray datasets
4
locus-based published
4
pre-existing microarray
4
mouse refseq
4
datasets transcriptional
4
sequencing data
4
3568 alternatively
4
alternatively spliced
4
spliced transcripts
4
deep rna
4
rna sequencing
4

References

(Supplied by CrossRef)

F Costantini et al.
Developmental cell 2010

M Little et al.
2010

KM Schmidt-Ott et al.
Journal of the American Society of Nephrology: JASN 2005

G Challen et al.
Physiological Genomics 2005

EW Brunskill et al.
Developmental Cell 2008

RO Stuart et al.
Proceedings of the National Academy of Sciences of the United States of America 2001

Z Wang et al.
Nat Rev Genet 2009

N Cloonan et al.
Genome biology 2008

E Birney et al.
Nature 2007

L Thorrez et al.
BMC genomics 2010

N Cloonan et al.
Nature methods 2008

Similar Publications