Clonal lineage determines the direct conversion of thalamic astrocytes into subtype-specific thalamocortical neurons
Forced expression of defined transcription factors leads to the direct conversion of various cell types into induced neurons (iNs). Specifically, successful reprogramming of resident brain astrocytes in vitro as well as in vivo represents a great advantage for the generation of neurons and derived circuits. However, whether astrocytes from distinct brain regions might show a reprogramming specificity towards a unique iN type remains largely unknown. Here, we use direct reprogramming of thalamic astrocytes by Neurog2 to generate specific excitatory sensory-modality thalamocortical neurons. Moreover, we show that the origin, but not the environment of the astrocytes determines the fate of the iNs after direct reprogramming. Indeed, clonal analysis in the thalamus shows that astrocytes from the distinct thalamic nuclei are clonally related determining the specificity of the iNs generated from those astrocytes. We also found that the potential of the same transcription factor to reprogram nuclei-specific thalamic astrocytes into precise subsets of thalamocortical neurons depends on particular epigenetic modifications. In sum, our study provides novel insights into the mechanisms that control the specification of thalamic neurons and importantly those that are required for direct programming of sensory neurons. Generation of specific sensory brain circuits might be an approach for future rehabilitation strategies.
Date: 6 December 2019, 13:00 (Friday, 8th week, Michaelmas 2019)
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: Large Lecture Theatre
Speaker: Professor Guillermina López-Bendito (Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), Sant Joan d’Alacant, Spain )
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser: Professor Zoltan Molnar (DPAG, University of Oxford)
Organiser contact email address:
Host: Professor Zoltan Molnar (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Talitha Smith