Author contributions: J.L.: conception and design, data analysis and interpretation, manuscript writing, financial support, and final approval of manuscript.; R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; S.S.K.: collection and assembly of data; C.F.: plasmid construction.
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1852–1862, September 2012
How to Cite
Filipovic, R., Santhosh Kumar, S., Fiondella, C. and Loturco, J. (2012), Increasing Doublecortin Expression Promotes Migration of Human Embryonic Stem Cell-Derived Neurons. STEM CELLS, 30: 1852–1862. doi: 10.1002/stem.1162
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 31, 2012.
- Issue published online: 20 AUG 2012
- Article first published online: 20 AUG 2012
- Accepted manuscript online: 29 JUN 2012 01:54PM EST
- Manuscript Accepted: 31 MAY 2012
- Manuscript Received: 4 MAR 2012
- Connecticut Stem Cell Initiative
- Human embryonic stem cells;
- Neuronal progenitor;
- Radial glia
Human embryonic stem cell-derived neuronal progenitors (hNPs) provide a potential source for cellular replacement following neurodegenerative diseases. One of the greatest challenges for future neuron replacement therapies will be to control extensive cell proliferation and stimulate cell migration of transplanted cells. The doublecortin (DCX) gene encodes the protein DCX, a microtubule-associated protein essential for the migration of neurons in the human brain. In this study, we tested whether increasing the expression of DCX in hNPs would favorably alter their proliferation and migration. Migration and proliferation of hNPs was compared between hNPs expressing a bicistronic DCX/IRES-GFP transgene and those expressing a green fluorescent protein (GFP) transgene introduced by piggyBac-mediated transposition. The DCX-transfected hNPs showed a significant decrease in their proliferation and migrated significantly further on two different substrates, Matrigel and brain slices. Additionally, a dense network of nestin-positive (+) and vimentin+ fibers were found to extend from neurospheres transplanted onto brain slices, and this fiber growth was increased from neurospheres containing DCX-transfected hNPs. In summary, our results show that increased DCX expression inhibits proliferation and promotes migration of hNPs. Stem Cells2012;30:1852–1862