DEVELOPMENT AND DISEASE
Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation
Hans Jörg Fehling1, Georges Lacaud2, Atsushi Kubo2, Marion Kennedy2, Scott Robertson3, Gordon Keller2,* and Valerie Kouskoff2
1 Department of Immunology, Medical Faculty/University Clinics Ulm, Germany
2 Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
3 Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA
* Author for correspondence (e-mail: gordon.k[email protected]
The hematopoietic and endothelial lineages derive from mesoderm and are thought to develop through the maturation of a common progenitor, the hemangioblast. To investigate the developmental processes that regulate mesoderm induction and specification to the hemangioblast, we generated an embryonic stem cell line with the green fluorescent protein (GFP) targeted to the mesodermal gene, brachyury. After the in vitro differentiation of these embryonic stem cells to embryoid bodies, developing mesodermal progenitors could be separated from those with neuroectoderm potential based on GFP expression. Co-expression of GFP with the receptor tyrosine kinase Flk1 revealed the emergence of three distinct cell populations, GFP-Flk1-, GFP+Flk1- and GFP+Flk1+ cells, which represent a developmental progression ranging from pre-mesoderm to prehemangioblast mesoderm to the hemangioblast.
Key words: ES cell, Brachyury, Mesoderm, Hemangioblast
Development 130, 4217-4227 (2003). © The Company of Biologists Limited.