Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 21 MAR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 3, pages 462–473, March 2011
How to Cite
Goulburn, A. L., Alden, D., Davis, R. P., Micallef, S. J., Ng, E. S., Yu, Q. C., Lim, S. M., Soh, C.-L., Elliott, D. A., Hatzistavrou, T., Bourke, J., Watmuff, B., Lang, R. J., Haynes, J. M., Pouton, C. W., Giudice, A., Trounson, A. O., Anderson, S. A., Stanley, E. G. and Elefanty, A. G. (2011), A Targeted NKX2.1 Human Embryonic Stem Cell Reporter Line Enables Identification of Human Basal Forebrain Derivatives. STEM CELLS, 29: 462–473. doi: 10.1002/stem.587
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: A.L.G.: design, collection, assembly, analyses and interpretation of data, manuscript writing; D.A., R.P.D., S.J.M., S.M.L, C-L.S., Q.C.Y., D.A.E., E.S.N., T.H., J.B., and B.W.: collection and analyses of data; R.J.L., J.M.H., and C.W.P.: design, collection, and interpretation of data, manuscript writing; A.G.: conception and design, collection of data; A.O.T.: conception and design; S.A.A.: design, collection and interpretation of data, manuscript writing; E.G.S. and A.G.E.: design, assembly, analyses and interpretation of data, manuscript writing and financial support.
First published online in STEM CELLSEXPRESS January 7, 2011; available online without subscription thorugh the open access option.
- Issue published online: 21 MAR 2011
- Article first published online: 21 MAR 2011
- Accepted manuscript online: 7 JAN 2011 03:31PM EST
- Manuscript Accepted: 7 DEC 2010
- Manuscript Received: 10 JUL 2010
- Australian Stem Cell Centre (ASCC)
- The National Health and Medical Research Council (NHMRC) of Australia
- The Juvenile Diabetes Research Foundation and the Starr Foundation
- Human embryonic stem cells;
- Ventral telencephalon;
- Retinoic acid;
We have used homologous recombination in human embryonic stem cells (hESCs) to insert sequences encoding green fluorescent protein (GFP) into the NKX2.1 locus, a gene required for normal development of the basal forebrain. Generation of NKX2.1-GFP+ cells was dependent on the concentration, timing, and duration of retinoic acid treatment during differentiation. NKX2.1-GFP+ progenitors expressed genes characteristic of the basal forebrain, including SHH, DLX1, LHX6, and OLIG2. Time course analysis revealed that NKX2.1-GFP+ cells could upregulate FOXG1 expression, implying the existence of a novel pathway for the generation of telencephalic neural derivatives. Further maturation of NKX2.1-GFP+ cells gave rise to γ-aminobutyric acid-, tyrosine hydroxylase-, and somatostatin-expressing neurons as well as to platelet-derived growth factor receptor α-positive oligodendrocyte precursors. These studies highlight the diversity of cell types that can be generated from human NKX2.1+ progenitors and demonstrate the utility of NKX2.1GFP/w hESCs for investigating human forebrain development and neuronal differentiation. STEM CELLS 2011;29:462–473