Gli1 Is an Inducing Factor in Generating Floor Plate Progenitor Cells from Human Embryonic Stem Cells
Författare
Summary, in English
Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and displayed exocrine SHH activity by ventrally patterning the surrounding neural progenitors. This system results in 63% FOXA2+ cells at the neural progenitor stage of hESC differentiation. The GLI1-transduced cells were also able to differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates that GLI1 is a determinant of FP specification in hESC and describes a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer. STEM CELLS 2010; 28: 1805-1815
Publiceringsår
2010
Språk
Engelska
Sidor
1805-1815
Publikation/Tidskrift/Serie
Stem Cells
Volym
28
Issue
10
Dokumenttyp
Artikel i tidskrift
Förlag
AlphaMed Press
Ämne
- Cell and Molecular Biology
Nyckelord
- Dopamine neuron
- Parkinson's disease
- GLI1
- Human embryonic stem cell
Status
Published
Forskningsgrupp
- Neurobiology
ISBN/ISSN/Övrigt
- ISSN: 1549-4918