Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons

• DOI: 10.1371/journal.pbio.1000373
• Publication Date: 2010-05-18T19:53:09Z
• Authors: Christophe Heinrich; Robert Blum; Sergio Gascón; Giacomo Masserdotti; Pratibha Tripathi; Rodrigo Sánchez; Steffen Tiedt; Timm Schroeder; Magdalena Götz; Benedikt Berninger
• Keywords: Reprogramming; Cell fate determination; Ganglionic eminence; Neurosphere; Interneuron

Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use endogenous astroglia for brain repair. However, previous attempts astroglia-derived failed establish functional synapses, severe limitation neurogenesis. It remained therefore also unknown whether derived could directed distinct neuronal subtype identities by selective fate determinants. Here we show that strong and persistent determinants driven silencing-resistant retroviral vectors instructs mature into fully functional, synapse-forming neurons. Importantly, neurotransmitter choice controlled factors: dorsal telencephalic determinant neurogenin-2 (Neurog2) directs cortical glutamatergic neurons; contrast, ventral Dlx2 induces GABAergic identity, although overall efficiency Dlx2-mediated reprogramming is much lower compared Neurog2, suggesting possess higher competence respond determinant. Interestingly, however, generation was greatly facilitated when astroglial cells were first expanded as neurosphere prior transduction with Dlx2. this approach expansion under conditions subsequent factors extended reactive isolated adult injured cortex, allowing or These data provide evidence undergo conversion across cell lineages single factor, stably generating differentiated Moreover, not restricted stages but achieved terminally injury-induced reactivation.