Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation

Ghanbarian, Hossein; Wagner, Nicole; Michiels, Jean‐François; Cuzin, François; Wagner, Kay-Dietrich; Rassoulzadegan, Minoo

doi:10.1038/srep41799

Cited by 20 publications

(48 citation statements)

References 20 publications

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“…Cdk9 plays a complex role in the myocardial differentiation, not only by association as a member of the p300/GATA4 complex to modulate the level of cardiac genes expression but also as a main core of P‐TEFb complex in activating RNAPII and inducing MRFs . Recently, we have recommended that transient induction of Cdk9 via ncRNAs with the sequences of Cdk9 results in efficient cardiac differentiation . Additionally, we have shown Cdk9 regulatory function on myogenic genes and myomiRs in C2C12 myoblast cells .…”

Section: Discussionmentioning

confidence: 86%

“…Muscle development (differentiation) is a multi‐step pathway. Myogenic regulatory factors (MRFs) and also small noncoding RNAs (ncRNAs) have a critical function in the control of this multi‐step pathway . MRFs including MyoD (myoblast determination protein), Myogenic and Mef2 (myocyte enhancer factor‐2) are expressed in different stages of myogenesis to create appropriate cardiac development .…”

Section: Introductionmentioning

confidence: 99%

“…As a mechanism for motivation of MRFs, Cdk9 interacts and phosphorylates MyoD , a muscle‐specific helix‐loop‐helix myogenic factor . Recently, we have reported that transient induction of Cdk9 by ncRNAs targeting Cdk9 sequence results in efficient cardiac differentiation . Moreover, we identified that Cdk9 has regulatory roles on myomiRs in mouse skeletal muscle cell line (C2C12 cells) .…”

Section: Introductionmentioning

confidence: 99%

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Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Tarhriz

Eyvazi

Musavi

et al. 2019

J of Cellular Biochemistry

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Cdk9 is a serine‐threonine protein kinase that has been recognized as a regulator of cardiac differentiation. Recently, we have reported that transient induction of Cdk9 using noncoding RNA targeting Cdk9 sequences results in efficient cardiac differentiation. Concerning Cdk9 regulatory roles, here, we proposed whether constant overexpression of Cdk9 might influence the differentiation of myoblast C2C12 cells into myotubes. We overexpressed Cdk9 in mouse myoblast C2C12 cells to investigate its regulatory roles on myogenic differentiation. Upon Cdk9 overexpression, the expression level of myogenic regulatory factors was determined. Moreover, the expression profile of three important myomiRs consist of miR 1, 133 and 206 was examined during the differentiation process. Although Cdk9 expression is necessary for inducing differentiation in the early stage of myogenesis, continuous Cdk9 expression inhibits differentiation by modulating myomiRs and myogenic gene expression. Our results indicate that the transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Tarhriz

Eyvazi

Musavi

et al. 2019

J of Cellular Biochemistry

Self Cite

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“…Other studies have reported that injection of short (20–22 nt) RNA fragments from a specific mRNA leads to increased transcription of the corresponding locus [120, 121]. Mechanistically, the authors report that the injected sense RNA fragments can form double-stranded RNA (dsRNA) duplexes with short antisense transcripts normally produced from the locus.…”

Section: Introductionmentioning

confidence: 99%

Genetic compensation: A phenomenon in search of mechanisms

2017

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Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.

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“…Biochemical approaches to regulate stem cell fate with readily available and inexpensive synthetic bioactive molecules may rectify these problems [14]. Many small molecules regulate the cellular processes of cardiomyocyte differentiation by modulating signal transduction pathways, including the canonical Wnt/β-catenin pathway [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Generation of a Urine-Derived Ips Cell Line from a Patient with a Ventricular Septal Defect and Heart Failure and the Robust Differentiation of These Cells to Cardiomyocytes via Small Molecules

Cao

Wen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ventricular septal defects (VSDs) are one of the most common types of congenital heart malformations. Volume overload resulting from large VSDs can lead to heart failure (HF) and constitutes a major cause of pediatric HF with a series of often-fatal consequences. The etiology of VSD with HF is complex, and increasing evidence points toward a genetic basis. Indeed, we identified an L2483R mutation in the ryanodine receptor type 2 (RyR2) in a 2-month-old male patient with VSD with HF. Methods: We generated integration-free induced pluripotent stem cells from urine samples (UiPSCs) of this patient using Sendai virus containing the Yamanaka factors and characterized these cells based on alkaline phosphatase activity, pluripotency marker expression, and teratoma formation. Then, we induced the derived UiPSCs to rapidly and efficiently differentiate into functional cardiomyocytes through temporal modulation of canonical Wnt signaling with small molecules. Real-time PCR and immunofluorescence were used to verify the expression of myocardium-specific markers in the differentiated cardiomyocytes. The ultrastructure of the derived myocardial cells was further analyzed by using transmission electron microscopy. Results: The established UiPSC lines were positive for alkaline phosphatase activity, retained the RyR2 mutation, expressed pluripotency markers, and displayed differentiation potential to three germ layers in vivo. The UiPSC-derived cells showed hallmarks of cardiomyocytes, including spontaneous contraction and strong expression of cardiac-specific proteins and genes. However, compared with cardiomyocytes derived from H9 cells, they had a higher level of autophagy, implying that autophagy may play an important role in the development of VSD with HF. Conclusion: The protocol described here yields abundant myocardial cells and provides a solid platform for further investigation of the pathogenesis, pharmacotherapy, and gene therapy of VSD with HF.

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Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation

Cited by 20 publications

References 20 publications

Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Genetic compensation: A phenomenon in search of mechanisms

Generation of a Urine-Derived Ips Cell Line from a Patient with a Ventricular Septal Defect and Heart Failure and the Robust Differentiation of These Cells to Cardiomyocytes via Small Molecules

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