Wnt1 overexpression leads to enforced cardiomyogenesis and inhibition of hematopoiesis in murine embryonic stem cells.
Recent findings emphasized a critical role for the Wnt signaling pathway during the early steps of embryogenesis, including the development of the hematopoietic system and cardiac development. To date, the role of Wnt in promoting or inhibiting development of both tissues was discussed controversially, dependent on species and time point of expression. Differentiation of embryonic stem cells (ESC) recapitulates early stages of mammalian development. In the present study, we generated murine ESC lines overexpressing Wnt1 (Wnt1 ES). When induced to differentiate toward the cardiomyocytic lineage, Wnt1 ES showed a significant increased ability to generate cardiomyocytes when compared with a control ESC (control ES) line. In addition, Wnt1 ES cells were unable to form hematopoietic cells, whereas development of endothelial cells, a cell type closely associated with blood during embryogenesis, was comparable to control ES. Finally, cardiac differentiation was markedly decreased by the addition of the Wnt antagonist Dkk-1 to the culture medium. These findings suggest that Wnt1 may regulate differentiation of immature mesodermal cells in a tissue-specific manner.
University of Tübingen, Medical Center, Department of Hematology, Oncology and Immunology, Tübingen, Germany. katja.weisel@med.uni-tuebingen.de
Katja C
KC
Weisel
Hans-Georg
HG
Kopp
Malcolm A S
MA
Moore
Lorenz
L
Studer
Tiziano
T
Barberi
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology*; D006410:Hematopoiesis; D051379:Mice; D024510:Muscle Development; D032383:Myocytes, Cardiac / Q000166:cytology*; D051155:Wnt1 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse