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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1515-1523.
Prepublished online as a Blood First Edition Paper on April 27, 2006; DOI 10.1182/blood-2005-11-011874.
Previous Article | Next Article 
Submitted November 30, 2005
Accepted April 18, 2006
Definitive-like erythroid cells derived from human
embryonic stem cells co-express high levels of embryonic
and fetal globins with little or no adult globin
Kai-Hsin Chang, Angelique M Nelson, Hua Cao, Linlin Wang, Betty Nakamoto, Carol B Ware, and Thalia Papayannopoulou*
University of Washington, Department of Medicine, Hematology division, Seattle, WA
University of Washington, Department of Comparative Medicine, Seattle, WA
University of Washington, Department of Medicine, Medical Genetics division, Seattle, WA
* Corresponding author; email: thalp{at}u.washington.edu.
Human embryonic stem cells are a promising tool to study
events associated with the earliest ontogenetic stages
of hematopoiesis. We describe the generation of
erythroid cells from hES (H1) by subsequent processing
of cells present at early and late stages of EB
differentiation. Kinetics of hematopoietic marker
emergence suggest that CD45(+) hematopoiesis
peaks at late D14EB differentiation stages, although low
level CD45(-) erythroid differentiation can
be seen before that stage. By morphologic criteria, hES-
derived erythroid cells were of definitive type, but
these cells both at mRNA and protein levels co-expressed
high levels of embryonic ( ) and fetal ( ) globins, with little or no adult globin ( ). This globin expression pattern was not altered
by the presence or absence of fetal bovine serum,
vascular endothelial growth factor, Flt3-L, or coculture
with OP-9, during erythroid differentiation and was not
culture time dependent. The co-expression of both
embryonic and fetal globins by definitive type erythroid
cells does not faithfully mimic either yolk sac
embryonic or their fetal liver counterparts.
Nevertheless, the high frequency of erythroid cells co-
expressing embryonic and fetal globin generated from ES
cells can serve as an invaluable tool to further explore
molecular mechanisms.

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