학술논문
A Targeted NKX2.1Human Embryonic Stem Cell Reporter Line Enables Identification of Human Basal Forebrain Derivatives
Document Type
Article
Author
Goulburn, Adam L.; Alden, Darym; Davis, Richard P.; Micallef, Suzanne J.; Ng, Elizabeth S.; Yu, Qing C.; Lim, Sue Mei; Soh, Chew‐Li; Elliott, David A.; Hatzistavrou, Tanya; Bourke, Justin; Watmuff, Bradley; Lang, Richard J.; Haynes, John M.; Pouton, Colin W.; Giudice, Antonietta; Trounson, Alan O.; Anderson, Stewart A.; Stanley, Edouard G.; Elefanty, Andrew G.
Source
Stem Cells; March 2011, Vol. 29 Issue: 3 p462-473, 12p
Subject
Language
ISSN
10665099; 15494918
Abstract
We have used homologous recombination in human embryonic stem cells (hESCs) to insert sequences encoding green fluorescent protein (GFP) into the NKX2.1locus, 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 FOXG1expression, 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/whESCs for investigating human forebrain development and neuronal differentiation. STEMCELLS2011;29:462–473