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| Status |
Public on Jan 30, 2013 |
| Title |
Braveheart is a long non-coding RNA necessary for cardiac lineage commitment |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: Long non-coding RNAs (lncRNAs) display development-specific gene expression patterns, yet we know little about their precise roles in lineage commitment. Here, we discover a novel mammalian heart-associated lncRNA, AK143260, necessary for cardiac lineage specification.
Methods: Gene expression profiles of mouse ESCs and differentiated organs were analyzed for master regulators of lineage commitment. The AK143260 transcript was shown to be strongly expressed in mESCs and in cells undergoing cardiac differentiation. Its role in cardiac differentiation was examined using depletion and in vitro differentiation systems, with morphological and gene expression profiling at different time-points.
Results: mESCs depleted of AK143260, named Braveheart, fail to differentiate into cardiomyocytes and to activate a core cardiac gene regulatory network including key transcription factors driving cardiogenesis. We show that Braveheart functions upstream of MesP1 (mesoderm posterior 1), a transcription factor critical for specification of the earliest known multi-potent cardiovascular progenitor and in promoting epithelial-mesenchymal transition (EMT). Consistent with this, Braveheart depletion leads to morphological defects and loss of cardiogenic potential in a defined in vitro cardiomyocyte differentiation system. Furthermore, Braveheart is necessary to maintain myocardial gene expression and myofibril organization in neonatal cardiomyocytes.
Conclusions: These findings reveal that Braveheart is an important regulator of cardiac commitment and implicate lncRNAs as potential therapeutic targets for cardiac disease and regeneration.
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| Overall design |
Gene expression profiles from control and Bravheart-depleted mESCs were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at Days 0,3,6 and 9.
Gene expression profiles from mESCs, MEFs, partially reprogrammed MEFs and miPS cells were obtained by RNA-Seq on Illumina GAII/GAIIx instruments.
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| Contributor(s) |
Klattenhoff C, Tabebordbar M, Boyer LL |
| Citation(s) |
23352431 |
| Submission date |
Jul 25, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Laurie A Boyer |
| E-mail(s) |
lboyer@mit.edu
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| Phone |
617 324-3335
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| Organization name |
Massachusetts Institute of Technology
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| Department |
Biology
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| Lab |
Boyer
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| Street address |
77 Massachusetts Avenue
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (3) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA171341 |
| SRA |
SRP014579 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39656_GSM1000592-GSM1000599_Discovery_RPKM.txt.gz |
4.4 Mb |
(ftp)(http) |
TXT |
| GSE39656_Time_Course_RPKMs.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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