miRNAs in ESC differentiation

Berardi, Emanuele; Pues, Matthias; Thorrez, Lieven; Sampaolesi, Maurilio

doi:10.1152/ajpheart.00338.2012

Cited by 41 publications

(36 citation statements)

References 69 publications

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“…The G1/S transition is regulated by the cyclin D-Cdk4, 6 and cyclin E-Cdk2 complexes. The cyclin D-Cdk4, 6 complex is not present in mouse ESCs; however, the cyclin E-Cdk2 complex that induces S phase and DNA replication is present and active [20,37] . In vivo experiments performed in a developing lung demonstrated that miR-302-367 decreased the expression of inhibitors of cdkn1a (p21) and Rbl2, inhibitors of the cyclin E-Cdk2 complex, which resulted in the formation of an undifferentiated multi-layered lung endoderm [38] .…”

Section: Micrornas In Maintenancementioning

confidence: 97%

“…Interestingly, the first two miRNAs discovered, lin-4 and let-7, were characterized during the developmental stage transition in C. elegans [16,17] . By deleting enzymes involved in miRNA processing and maturation, namely, Dicer or Dgcr8, studies have shown that miRNAs are important in maintaining ESC pluripotency and differentiation capacity [18][19][20] . miRNAs also play a role in the differentiation and self-renewal of mesenchymal stem cells (MSCs) [21] .…”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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Section: Micrornas In Maintenancementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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“…miRNAs have been shown to be essential for ESC differentiation, and a number have been shown to be directly involved in the directed differentiation of ESCs to specific lineages. 14 An RNAi screen set out to identify novel regulators of ESC self-renewal identified a wide selection of mRNAs that when knocked down, induce ESCs to differentiate. Interestingly, a significant number of these were RNA regulators, implicating post-transcriptional control in selfrenewal and differentiation.…”

Section: A Role For Polyamine Regulators In Esc Self-renewalmentioning

confidence: 99%

A role for polyamine regulators in ESC self-renewal

Zhao

Goh

et al. 2012

Cell Cycle

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E mbryonic stem cells (ESCs) dependon extensive regulatory networks to coordinate their self-renewal and differentiation. The polyamine pathway regulator AMD1 was recently implicated in ESC self-renewal and directed differentiation of ESCs to neural precursor cells (NPCs). The polyamines spermine and spermidine are essential for a wide range of biological processes, and their levels are tightly regulated. Here, we review the polyamine pathway and discuss how it can impact polyamine levels, cellular methylation and hypusinated EIF5A levels. We discuss how it could feed into regulation of ESC self-renewal and directed differentiation. We show that in addition to AMD1, a second rate-limiting enzyme in the polyamine pathway, ODC1, can also promote ESC self-renewal, and that both Amd1 and Odc1 can partially substitute for Myc during cellular reprogramming. We propose that both Amd1 and Odc1 are essential regulators of ESCs and function to ensure high polyamine levels to promote ESC self-renewal.

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“…For example, aberrant methylation in cancer is frequently observed 6 and the distinct patterns of promoter methylation between monozygotic (MZ) twin pairs have also been found to result in different health conditions 7 . In contrast to DNA methylation, miRNA regulation of target genes is more flexible and can change even during cellular differentiation 8 . miRNA expression is often tissue-specific, and similar to DNA methylation, miRNA expression has been linked to human disease 9 .…”

Section: Introductionmentioning

confidence: 99%

Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

Taguchi

2013

F1000Res

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Science and Technology Norway Discuss this article AbstractmiRNA regulation of target genes and promoter methylation are Background known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied.Gene expression and promoter methylation profiles of 271 distinct Methods human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeted-gene promoter methylaion and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Significant changes in promoter methylation were associated with Results miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs.It was found that promoter methylation was affected by miRNA Conclusions targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation is suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).

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miRNAs in ESC differentiation

Cited by 41 publications

References 69 publications

MicroRNAs as novel regulators of stem cell fate

MicroRNAs as novel regulators of stem cell fate

A role for polyamine regulators in ESC self-renewal

Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

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