Mini-Seminar: Stem Cell Center invites Swedish researchers

28 January 2013

Tuesday February 12, 11:00-13:00
A3.3067, Rikshospitalet
Snacks will be provided between the speeches. 

Johan Jakobsson
Faculty of Medicine, Lund University
Title: miR-124–determination of neuronal identity by a non-coding RNA

MicroRNAs (miRNAs) are small, noncoding, endogenous RNA that bind to and regulate mRNA targets, making them central players of gene regulation. In neurons, microRNA-124 (miR-124) is one of the most abundant miRNAs. We have during the recent years studied the role of miR-124 using /in vivo/ models.

By developing a transgenic reporter mouse that allows visualization of miR-124 activity in the brain /in vivo/ we have found that in the SVZ stem cell niche, miR-124 activity is initiated in transient amplifying progenitors, type C cells. This finding was substantiated with loss of function studies of miR-124 in the SVZ, demonstrating that stable inhibition of this miRNA does not force progenitors to remain cycling. miR-124 loss of function, rather, blocks adult neurogenesis and induces the formation of ectopic astrocytes in the OB derived from the SVZ.

In mature neurons miR-124 appears to regulate synaptic plasticity. Loss of function experiments coupled with behavioral analysis show that reduction of miR-124-levels is associated with better performance in working memory tasks.

In summary, these data suggest that miR-124 plays a vital role both in the formation of new neurons as well as regulating neuronal function.

Malin Parmar
Faculty of Medicine, Lund University
Title: Developing Stem Cells for Cell Replacement Therapy in Parkinson’s Disease

Parkinson’s Disease (PD) is a particularly interesting target for stem cell based therapy. The central pathology is confined to a small group of neurons in the midbrain, the nigral dopamine (DA) neurons and their projection to the striatum. Transplants of DA neurons could be used to restore DA neurotransmission in the striatum, substitute for the lost neurons, and bring back normal motor behavior. Proof-of-principle that this can work has been obtained in trials where fetal DA neuroblasts, have been transplanted to the putamen in patients with advanced PD. Despite these encouraging results, work with human fetal tissue presents a number of ethical and logistical problems and therefore does not represent a realistic therapeutic option in the future. Further progress in this field is critically dependent on the development of a bankable and renewable source of transplantable DA neurons.

We have developed a method to generate human neural progenitors and neurons from human embryonic stem cells (hESCs), which recapitulates human fetal brain development. By addition of a small molecule to activate canonical WNT signalling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. The DA neurons obtained via our protocol closely resembled their fetal counterparts, making them useful as a model system for studies of human fetal brain development and also for developing transplantable
therapeutic cells.

In parallel, we also develop cell reprogramming as an alternative source of neurons. We have found that the neural conversion genes (Mash1, Brn2a, Myt1l) can convert human fibroblasts into induced neurons (iNs). When combined with DA fate determinants, functional DA neurons can be obtained with this technique.