The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Gli1 Is an Inducing Factor in Generating Floor Plate Progenitor Cells from Human Embryonic Stem Cells

På svenska

Author

  • Mark Denham
  • Lachlan Thompson
  • Jessie Leung
  • Alice Pebay
  • Anders Björklund
  • Mirella Dottori

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

Publishing year

2010

Language

English

Pages

1805-1815

Publication/Series

Stem Cells

Volume

28

Issue

10

Document type

Journal article

Publisher

AlphaMed Press

Topic

  • Cell and Molecular Biology

Keywords

  • Dopamine neuron
  • Parkinson's disease
  • GLI1
  • Human embryonic stem cell

Status

Published

Research group

  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 1549-4918