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 and Ramos Gomez, Milagros and Courtois, Elise T. and Tonnesen, Jan and Kokaia, Merab and Liste, Isabel and 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.

Description

Title: Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL
Author/s:
  • Gonzalez Seiz, Emma
  • Ramos Gomez, Milagros
  • Courtois, Elise T.
  • Tonnesen, Jan
  • Kokaia, Merab
  • Liste, Isabel
  • Martinez Serrano, Alberto
Item Type: Article
Título de Revista/Publicación: Experimental Cell Research
Date: November 2012
ISSN: 0014-4827
Volume: 318
Subjects:
Freetext Keywords: Substantia nigra precursors; Floor plate; Neuron maturation; Bcl-XL; Neural development; Parkinson's disease cell therapy
Faculty: E.T.S.I. Telecomunicación (UPM)
Department: Tecnología Fotónica [hasta 2014]
Creative Commons Licenses: Recognition - No derivative works - Non commercial

Full text

[img]
Preview
PDF - Requires a PDF viewer, such as GSview, Xpdf or Adobe Acrobat Reader
Download (6MB) | Preview

Abstract

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.

More information

Item ID: 16732
DC Identifier: http://oa.upm.es/16732/
OAI Identifier: oai:oa.upm.es:16732
DOI: 10.1016/j.yexcr.2012.07.018
Official URL: http://www.sciencedirect.com/science/article/pii/S0014482712003606
Deposited by: Memoria Investigacion
Deposited on: 07 Aug 2013 16:58
Last Modified: 21 Apr 2016 17:05
  • Logo InvestigaM (UPM)
  • Logo GEOUP4
  • Logo Open Access
  • Open Access
  • Logo Sherpa/Romeo
    Check whether the anglo-saxon journal in which you have published an article allows you to also publish it under open access.
  • Logo Dulcinea
    Check whether the spanish journal in which you have published an article allows you to also publish it under open access.
  • Logo de Recolecta
  • Logo del Observatorio I+D+i UPM
  • Logo de OpenCourseWare UPM