Memorias de investigación
Artículos en revistas:
Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL
Año:2012
Áreas de investigación
  • Ciencias naturales y ciencias de la salud,
  • Tecnología electrónica y de las comunicaciones
Datos
Descripción
Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson?s disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-XL induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-XL anticipates and enhances DAn generation.
Internacional
Si
JCR del ISI
Si
Título de la revista
Experimental Cell Research
ISSN
0014-4827
Factor de impacto JCR
3,58
Información de impacto
Volumen
318
DOI
Número de revista
Desde la página
2446
Hasta la página
2459
Mes
AGOSTO
Ranking
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Participantes
Grupos de investigación, Departamentos, Centros e Institutos de I+D+i relacionados
  • Creador: Grupo de Investigación: Grupo de Bioingeniería y Telemedicina
  • Centro o Instituto I+D+i: Centro de tecnología Biomédica CTB
  • Departamento: Tecnología Fotónica y Bioingeniería