期刊
STEM CELLS
卷 29, 期 3, 页码 462-473出版社
WILEY
DOI: 10.1002/stem.587
关键词
Human embryonic stem cells; NKX2.1; FGF; Ventral telencephalon; Hypothalamus; Retinoic acid; MGE
资金
- Australian Stem Cell Centre (ASCC)
- National Health and Medical Research Council (NHMRC) of Australia
- Juvenile Diabetes Research Foundation
- Starr Foundation
- NHMRC
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 gamma-aminobutyric acid-, tyrosine hydroxylase-, and somatostatin-expressing neurons as well as to platelet-derived growth factor receptor a-positive oligodendrocyte precursors. These studies highlight the diversity of cell types that can be generated from human NKX2.1 1 progenitors and demonstrate the utility of NKX2.1(GFP/w) hESCs for investigating human forebrain development and neuronal differentiation. STEM CELLS 2011;29:462-473
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