EURON and THEME joint PhD meeting
EURON and THEME joint PhD meeting
EURON and THEME joint PhD meeting
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86<br />
<strong>EURON</strong> <strong>and</strong> <strong>THEME</strong> <strong>joint</strong> <strong>meeting</strong> 2011<br />
The impact of bifunctional microRNA-9/9* on the<br />
differentiation of human ES cell – derived neural stem<br />
cells<br />
Beate Roese-Koerner, Lodovica Borghese, Laura Mürtz, Oliver Brüstle<br />
Institute for Reconstructive Neurobiology, University of Bonn.<br />
MicroRNAs are non-coding RNA molecules about 22 nucleotide-long that<br />
regulate gene expression at a post-transcriptional level. MicroRNAs are known<br />
to be involved in many cellular processes including stem cell self-renewal <strong>and</strong><br />
differentiation. We carried out a comparative microRNA expression profiling<br />
across the differentiation of human embryonic stem cells (hESC) into neural<br />
stem cells (lt-NES®) <strong>and</strong> their neuronal progeny. MicroRNA-9/9* (miR-9/9*) was<br />
among the microRNAs that showed a strikingly differential expression pattern.<br />
It was barely detectable in hESC, whereas it was found expressed in lt-NES® <strong>and</strong><br />
up-regulated in differentiating neurons.<br />
To gain insight into the potential roles of miR-9/9* in our long-term self-renewing<br />
lt-NES®, we made use of a lentiviral-based overexpression system <strong>and</strong> achieved<br />
overexpression of the mature forms of both miR-9 <strong>and</strong> miR-9* at comparable<br />
levels. Despite the presence of growth factors (i.e. FGF2 <strong>and</strong> EGF) in the culture<br />
medium, miR-9/9* overexpression induced a reduction in proliferation <strong>and</strong> an<br />
increase in differentiation of lt-NES®, as assessed by BrdU incorporation <strong>and</strong><br />
expression of neuronal markers. By exposing lt-NES® to individual synthetic<br />
mimics of miR-9 <strong>and</strong> miR-9*, we could demonstrate that the promotion of<br />
differentiation is due both to miR-9 <strong>and</strong> miR-9*, whereas the anti-proliferative<br />
effect is mainly exerted by miR-9* alone. We are currently investigating potential<br />
connections between miR-9/9* <strong>and</strong> signaling pathways that are relevant in<br />
neural stem cell maintenance <strong>and</strong> differentiation.<br />
Our experimental approach provides an elegant way to assess the role of<br />
microRNAs – including bifunctional ones such as miR-9/9* - during early human<br />
neural development. It further offers a promising tool for the modulation of<br />
microRNA levels to gain control on the fate of human stem cells.