Open AccessThe 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
Author(s) -
Cai Jingli,
Donaldson Angela,
Yang Ming,
German Michael S.,
Enikolopov Grigori,
Iacovitti Lorraine
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0734
Subject(s) - biology , embryonic stem cell , midbrain , dopamine , stem cell , transplantation , parkinson's disease , neuroscience , microbiology and biotechnology , cellular differentiation , disease , pathology , medicine , central nervous system , genetics , gene
Recent studies have provided important insight into the homeoprotein LIM homeobox transcription factor 1α (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. S TEM C ELLS 2009;27:220–229