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| Status |
Public on Dec 22, 2016 |
| Title |
RNA-seq analysis of retinoic acid treated mouse neuromesodermal progenitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2-/- embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages.
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| Overall design |
3 samples were analyzed in duplicate: DMSO control (2 hours), 25 nM retinoic acid (2 hours), 1 µM retinoic acid (2 hours)
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| Web link |
http://bio.biologists.org/content/5/12/1821.long
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| |
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| Contributor(s) |
Duester G, Cunningham TJ |
| Citation(s) |
27793834 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 GM062848 |
Generation of Retinoid Signals during Development: Generation of Retinoid Signals During Development: Generation of Retinoid Signals During Development: Generation of Retinoid Signals During Development: Generation of Retinoid Signals During Development: Generation of Retinoid Signals During Development: Generation of Retinoid Signals during Development: Generation of Retinoid Signals during Development: Generation of Retinoid Signals during Development: Generation of Retinoid Signals during Development |
Sanford-Burnham Medical Research Institute |
GREGG L DUESTER |
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| |
| Submission date |
Jun 13, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gregg Duester |
| E-mail(s) |
duester@sbpdiscovery.org
|
| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
|
| Street address |
10901 N. Torrey Pines Road
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA325436 |
| SRA |
SRP076453 |
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