Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Gonzalez Seiz, Emma; Ramos Gomez, Milagros; Courtois, Elise T.; Tonnesen, Jan; Kokaia, Merab; Liste, Isabel y Martinez Serrano, Alberto (2012). Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL. "Experimental Cell Research", v. 318 (n. 19); pp. 2446-2459. ISSN 0014-4827. https://doi.org/10.1016/j.yexcr.2012.07.018.

Descripción

Título: Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL
Autor/es:
  • Gonzalez Seiz, Emma
  • Ramos Gomez, Milagros
  • Courtois, Elise T.
  • Tonnesen, Jan
  • Kokaia, Merab
  • Liste, Isabel
  • Martinez Serrano, Alberto
Tipo de Documento: Artículo
Título de Revista/Publicación: Experimental Cell Research
Fecha: Noviembre 2012
Volumen: 318
Materias:
Palabras Clave Informales: Substantia nigra precursors; Floor plate; Neuron maturation; Bcl-XL; Neural development; Parkinson's disease cell therapy
Escuela: E.T.S.I. Telecomunicación (UPM)
Departamento: Tecnología Fotónica [hasta 2014]
Licencias Creative Commons: Reconocimiento - Sin obra derivada - No comercial

Texto completo

[img]
Vista Previa
PDF (Document Portable Format) - Se necesita un visor de ficheros PDF, como GSview, Xpdf o Adobe Acrobat Reader
Descargar (6MB) | Vista Previa

Resumen

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.

Más información

ID de Registro: 16732
Identificador DC: http://oa.upm.es/16732/
Identificador OAI: oai:oa.upm.es:16732
Identificador DOI: 10.1016/j.yexcr.2012.07.018
URL Oficial: http://www.sciencedirect.com/science/article/pii/S0014482712003606
Depositado por: Memoria Investigacion
Depositado el: 07 Ago 2013 16:58
Ultima Modificación: 21 Abr 2016 17:05
  • Open Access
  • Open Access
  • Sherpa-Romeo
    Compruebe si la revista anglosajona en la que ha publicado un artículo permite también su publicación en abierto.
  • Dulcinea
    Compruebe si la revista española en la que ha publicado un artículo permite también su publicación en abierto.
  • Recolecta
  • e-ciencia
  • Observatorio I+D+i UPM
  • OpenCourseWare UPM