Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation.
Microinjection of small noncoding RNAs in one-cell embryos was reported in several instances to result in transcriptional activation of target genes. To determine the molecular mechanisms involved and to explore whether such epigenetic regulations could play a role in early development, we used a cell culture system as close as possible to the embryonic state. We report efficient cardiac differentiation of embryonic stem (ES) cells induced by small non-coding RNAs with sequences of Cdk9, a key player in cardiomyocyte differentiation. Transfer of oligoribonucleotides representing parts of the Cdk9 mRNA into ES and mouse embryo fibroblast cultures resulted in upregulation of transcription. Dependency on Argonaute proteins and endogenous antisense transcripts indicated that the inducer oligoribonucleotides were processed by the RNAi machinery. Upregulation of Cdk9 expression resulted in increased efficiency of cardiac differentiation suggesting a potential tool for stem cell-based regenerative medicine.
Biotechnology Department, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hossein
H
Ghanbarian
Université Côte d'Azur, CNRS, INSERM, IRCAN, 06107, Nice, France.|Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
Nicole
N
Wagner
Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.|Department of Pathology, CHU Nice, Nice, France.
Jean-François
JF
Michiels
Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
François
F
Cuzin
Université Côte d'Azur, CNRS, INSERM, IRCAN, 06107, Nice, France.|Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
Kay-Dietrich
KD
Wagner
Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
Minoo
M
Rassoulzadegan
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D016372:RNA, Antisense; D058727:RNA, Small Untranslated / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D060565:Argonaute Proteins; D016372:RNA, Antisense; D058727:RNA, Small Untranslated; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D042863:Cyclin-Dependent Kinase 9