The Role of Lmx1a in the Differentiation of Human Embryonic Stem Cells into Midbrain Dopamine Neurons in Culture and After Transplantation into a Parkinson's Disease Model

Cai, J., Donaldson, A., Yang, M., German, M. S., Enikolopov, G. N., Iacovitti, L. (January 2009) The Role of Lmx1a in the Differentiation of Human Embryonic Stem Cells into Midbrain Dopamine Neurons in Culture and After Transplantation into a Parkinson's Disease Model. Stem Cells, 27 (1). pp. 220-229.

Abstract

Recent studies have provided important insight into the homeoprotein LIM homeobox transcription factor 1{alpha} (Lmx1a) and its role in the commitment of cells to a midbrain dopamine (mDA) fate in the developing mouse. We show here that Lmx1a also plays a pivotal role in the mDA differentiation of human embryonic stem (hES) cells. Thus, as indicated by small interfering RNA experiments, the transient early expression of Lmx1a is necessary for the coordinated expression of all other dopamine (DA)-specific phenotypic traits as hES cells move from multipotent human neural progenitor cells (hNPs) to more restricted precursor cells in vitro. Moreover, only Lmx1a-specified hNPs have the potential to differentiate into bona fide mDA neurons after transplantation into the 6-hydroxydopamine-treated rat striatum. In contrast, cortical human neuronal precursor cells (HNPCs) and mouse subventricular zone cells do not express Lmx1a or become mDA neurons even when placed in an environment that fosters their DA differentiation in vitro or in vivo. These findings suggest that Lmx1a may be critical to the development of mDA neurons from hES cells and that, along with other key early DA markers (i.e., Aldh1a1), may prove to be extremely useful for the selection of appropriately staged and suitably mDA-specified hES cells for cell replacement in Parkinson's disease. STEM CELLS 2009;27:220-229

Item Type:	Paper
Uncontrolled Keywords:	Lmx1a Human embryonic stem cells Dopamine neuron Differentiation
Subjects:	diseases & disorders diseases & disorders > nervous system diseases and disorders diseases & disorders > nervous system diseases and disorders > Parkinson's disease organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron organs, tissues, organelles, cell types and functions therapies > stem cells
CSHL Authors:	Enikolopov, Grigori N.
Communities:	CSHL labs > Enikopolov lab CSHL Cancer Center Shared Resources > Animal Services
Depositing User:	Matt Covey
Date:	1 January 2009
Date Deposited:	20 Feb 2013 14:37
Last Modified:	29 Dec 2014 16:37
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27446

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