Banca de QUALIFICAÇÃO: MALEK CHOUCHANE

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE: MALEK CHOUCHANE
DATA: 02/12/2015
HORA: 09:30
LOCAL: INSTITUTO DO CÉREBRO
TÍTULO:

Direct lineage-reprogramming of distinct astroglial population into neurons in vitro and in vivo

PALAVRAS-CHAVES:

astroglia, cell fate reprogramming, neurogenic transcription factors, cell transplant

PÁGINAS: 40
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Recently, the field of cellular reprogramming has been revolutionized by works showing the  potential to directly lineage-reprogram somatic cells into neurons upon overexpression of specific transcription factors. This technique offers a promising strategy to study the molecular mechanisms of neuronal specification, identify potential therapeutic targets for neurological diseases and eventually repair the central nervous system damaged by neurological conditions. Notably, studies with cortical astroglia revealed the high potential of these cells to reprogram into neurons using a single neuronal transcription factor. However, it remains unknown whether astroglia isolated from different regions of the central nervous system have the same neurogenic potential and if they will generate the same phenotype of induced neurons. In this study we investigate the potential to reprogram astroglial cells isolated from the postnatal cerebellum into functional neurons using the proneural transcription factors Neurogenin-2 (Neurog2) and Achaete scute homolog-1 (Ascl1). We also evaluated the capacity of astroglia isolated from the cerebral cortex or cerebellum and reprogrammed into induced neurons to integrate into a neurogenic (subventricular zone – SVZ) or non-neurogenic (cerebral cortex) milieu in vivo. We observed that cortical astroglia underwent a full process of neuronal reprogramming in the brain, independently of the region of transplant and the transcription factor used. However, induced neurons behaved differently when transplanted in the SVZ or cerebral cortex. While astroglia overexpressing Ascl1 or Neurog2 reprogrammed into induced neurons migrated through the rostral migratory stream and integrated in the olfactory bulb (OB), astroglia overexpressing Neurog2 and transplanted in the cerebral cortex converted into spiny pyramidal neurons. Collectively, our results indicate that astroglial cells isolated from different regions undergo a full process of lineage-reprogramming into induced neurons after transplantation in vivo. They also suggest that the region of transplant play instructive roles in the phenotypic specification of induced neurons.

MEMBROS DA BANCA:
Externo à Instituição - CECILIA HEDIN PEREIRA - UFRJ
Interno - 1871878 - KERSTIN ERIKA SCHMIDT
Presidente - 1674643 - MARCOS ROMUALDO COSTA