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Review
. 2013:786:329-51.
doi: 10.1007/978-94-007-6621-1_18.

Regulation of stem cell populations by microRNAs

Julie Mathieu  1 , Hannele Ruohola-Baker
Affiliations
Review

Regulation of stem cell populations by microRNAs

Julie Mathieu et al. Adv Exp Med Biol. 2013.

Abstract

miRNAs are small non-coding RNAs that have emerged as crucial post-transcriptional regulators of gene expression. They are key players in various critical cellular processes such as proliferation, cell cycle progression, apoptosis and differentiation. Self-renewal capacity and differentiation potential are hallmarks of stem cells. The switch between self-renewal and differentiation requires rapid widespread changes in gene expression. Since miRNAs can repress the translation of many mRNA targets, they are good candidates to regulate cell fates. In the past few years, miRNAs have appeared as important new actors in stem cell development by regulating differentiation and maintenance of stem cells. In this chapter we will focus on the role of miRNAs in various stem cell populations. After an introduction on microRNA biogenesis, we will review the recent knowledge on miRNA expression and function in pluripotent cells and during the acquisition of stem cell fate. We will then briefly examine the role of miRNAs in adult and cancer stem cells.

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Figures

Fig. 18.1
Fig. 18.1. microRNA biogenesis and function
miRNA genes are transcribed by RNA polymerase II or III and processed in two steps. The first step involved either the microprocessor containing Drosha and DGCR8 (canonical pathway) or the splicing machinery (mirtron pathway). The second cleavage is performed by Dicer for most mammalian miRNAs, but miR-451. Mature miRNAs assemble with the RISC complex and regulate gene expression by inhibiting translation, inducing mRNA degradation or, less commonly, upregulating translation. SR = seed region/seed sequence. See text for more details
Fig. 18.2
Fig. 18.2. Role of miRNAs in ESC self-renewal, proliferation and differentiation
ESCs express a unique signature of miRNAs whose transcription is regulated by a core pluripotency factors (Oct4, Sox2, Nanog). ESC-enriched miRNAs control the specific ESC cell cycle by targeting regulatory proteins involved in G1/S and G2/M transitions. ESC-enriched miRNAs maintain self-renewal capacities of ESCs as well as their pluripotency potential. Differentiated cells express miRNAs such as miR-145 and let-7 that target pluripotency factors and activate differentiation genes. Moreover, cell cycle inhibitors are expressed and cells exhibit a cell cycle dependent of the restriction point (R)
Fig. 18.3
Fig. 18.3. Functions of miRNAs in cellular reprogramming
(a) Overview of the effects of miRNAs on iPSC formation. miRNAs beneficial for iPSC induction are represented in red while miRNAs shown to repress iPSC formation are in green. In orange are the microRNAs whose function has not been tested yet during reprogramming of somatic cells into pluripotent stem cells. (b) Mechanisms of action of miRNAs during the reprogramming process. OSK: Oct4, Sox2, Nanog. MET mesenchymal to epithelial transition
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