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Series GSE39656 Query DataSets for GSE39656
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
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.
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.
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
Phone 617 324-3335
Organization name Massachusetts Institute of Technology
Department Biology
Lab Boyer
Street address 77 Massachusetts Avenue
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (3)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (20)
GSM976919 Scrambled Hairpin-treated mESCs D0
GSM976920 Scrambled Hairpin-treated mESCs D3
GSM976921 Scrambled Hairpin-treated mESCs D6
BioProject PRJNA171341
SRA SRP014579

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
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Raw data are available in SRA
Processed data are available on Series record

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