Open AccessIdentification and Characterization of Hemoangiogenic Progenitors During Cynomolgus Monkey Embryonic Stem Cell Differentiation
Author(s) -
Umeda Katsutsugu,
Heike Toshio,
Yoshimoto Momoko,
Shinoda Gen,
Shiota Mitsutaka,
Suemori Hirofumi,
Luo Hong Yuan,
Chui David H. K.,
Torii Ryuzo,
Shibuya Masabumi,
Nakatsuji Norio,
Nakahata Tatsutoshi
Publication year - 2006
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2005-0165
Subject(s) - biology , hemangioblast , progenitor cell , cd34 , embryonic stem cell , microbiology and biotechnology , endothelial stem cell , stem cell , haematopoiesis , cellular differentiation , immunology , genetics , in vitro , gene
We identified intermediate‐stage progenitor cells that have the potential to differentiate into hematopoietic and endothelial lineages from nonhuman primate embryonic stem (ES) cells. Sequential fluorescence‐activated cell sorting and immunostaining analyses showed that when ES cells were cultured in an OP9 coculture system, both lineages developed after the emergence of two hemoangiogenic progenitor‐bearing cell fractions, namely, vascular endothelial growth factor receptor (VEGFR)‐2 high CD34 − and VEGFR‐2 high CD34 + cells. Exogenous vascular endothelial growth factor increased the proportion of VEGFR‐2 high cells, particularly that of VEGFR‐2 high CD34 + cells, in a dose‐dependent manner. Although either population of VEGFR‐2 high cells could differentiate into primitive and definitive hematopoietic cells (HCs), as well as endothelial cells (ECs), the VEGFR‐2 high CD34 + cells had greater hemoangiogenic potential. Both lineages developed from VEGFR‐2 high CD34 − or VEGFR‐2 high CD34 + precursor at the single‐cell level, which strongly supports the existence of hemangioblasts in these cell fractions. Thus, this culture system allows differentiation into the HC and EC lineages to be defined by surface markers. These observations should facilitate further studies both on early developmental processes and on regeneration therapies in human.