The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification.

Laura Stappert,Oliver Brüstle,Beate Roese-Koerner

doi:10.1007/s00441-014-1981-y

Abstract

The impressive neuronal diversity found within the nervous system emerges from a limited pool of neural progenitor cells that proceed through different gene expression programs to acquire distinct cell fates. Here, we review recent evidence indicating that microRNAs (miRNAs) are critically involved in conferring neural cell identities during neural induction, neuronal differentiation and subtype specification. Several studies have shown that miRNAs act in concert with other gene regulatory factors and genetic switches to regulate the spatial and temporal expression profiles of important cell fate determinants. So far, most studies addressing the role of miRNAs during neurogenesis were conducted using animal models. With the advent of human pluripotent stem cells and the possibility to differentiate these into neural stem cells, we now have the opportunity to study miRNAs in a human context. More insight into the impact of miRNA-based regulation during neural fate choice could in the end be exploited to develop new strategies for the generation of distinct human neuronal cell types.

Highlights

Considered as “junk RNA”, non-coding RNAs are currently perceived as critical regulators of the cellular homeostasis
We focus on the impact of miRNAs during neural induction and exemplarily highlight the interaction of miR124 and miR-9 with important regulatory circuits and epigenetic regulators
We describe how miRNAs interact with spatial and temporal fate determinants to generate the neuronal diversity found in the central nervous system (CNS)

Summary

Introduction

Considered as “junk RNA”, non-coding RNAs are currently perceived as critical regulators of the cellular homeostasis (reviewed by Esteller 2011). MiR-200 acts on the same pathway and represses neural induction of hES cells by targeting the transcription factor ZEB–a negative regulator of BMP/TGFβ signaling (Du et al 2013). MiR-96 inhibits neural induction of hES cells by targeting the transcription factor PAX6 (Du et al 2013).

Results

Conclusion