|
|
Blood, 1 January 2008, Vol. 111, No. 1, pp. 122-131.
Prepublished online as a Blood First Edition Paper on September 17, 2007; DOI 10.1182/blood-2007-04-084186.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells
Petter S. Woll1,
Julie K. Morris1,
Matt S. Painschab1,
Rebecca K. Marcus1,
Aimee D. Kohn2,
Travis L. Biechele2,
Randall T. Moon2, and
Dan S. Kaufman1
1 Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis; and
2 Howard Hughes Medical Institute, Department of Pharmacology and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle
Human embryonic stem cells (hESCs) provide an important means to effectively study soluble and cell-bound mediators that regulate development of early blood and endothelial cells in a human model system. Here, several complementary methods are used to demonstrate canonical Wnt signaling is important for development of hESC-derived cells with both hematopoietic and endothelial potential. Analyses using both standard flow cy-tometry, as well the more detailed high-throughput image scanning flow cytometry, characterizes sequential development of distinct early developing CD34brightCD31+Flk1+ cells and a later population of CD34dimCD45+ cells. While the CD34brightCD31+Flk1+ have a more complex morphology and can develop into both endothelial cells and hematopoietic cells, the CD34dimCD45+ cells have a simpler morphology and give rise to only hematopoietic cells. Treatment with dickkopf1 to inhibit Wnt signaling results in a dramatic decrease in development of cells with hematoendothelial potential. In addition, activation of the canonical Wnt signaling pathway in hESCs by coculture with stromal cells that express Wnt1, but not use of noncanonical Wnt5-expressing stromal cells, results in an accelerated differentiation and higher percentage of CD34brightCD31+Flk1+ cells at earlier stages of differentiation. These studies effectively demonstrate the importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. S. Kaufman
Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells
Blood,
October 22, 2009;
114(17):
3513 - 3523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kim, Y. Kim, H.-T. Kim, D. W. Kim, Y. Ha, J. Kim, C.-H. Kim, I. Lee, and K. Song
TC1(C8orf4) Is a Novel Endothelial Inflammatory Regulator Enhancing NF-{kappa}B Activity
J. Immunol.,
September 15, 2009;
183(6):
3996 - 4002.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Woll, B. Grzywacz, X. Tian, R. K. Marcus, D. A. Knorr, M. R. Verneris, and D. S. Kaufman
Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity
Blood,
June 11, 2009;
113(24):
6094 - 6101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhou, P. Su, L. Wang, J. Chen, M. Zimmermann, O. Genbacev, O. Afonja, M. C. Horne, T. Tanaka, E. Duan, et al.
mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells
PNAS,
May 12, 2009;
106(19):
7840 - 7845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Martin, P. S. Woll, Z. Ni, J. C. Zuniga-Pflucker, and D. S. Kaufman
Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells
Blood,
October 1, 2008;
112(7):
2730 - 2737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
