Submitted August 19, 2008
Accepted March 8, 2009
Expression of SCL in mesoderm rescues hematopoiesis in the absence of Oct-4
Kimi Y. Kong, Elizabeth A. Williamson, Jason H. Rogers, Tam Tran, Robert Hromas, and Richard Dahl*
Department of Internal Medicine and the Cancer Research and Treatment Center, University of New Mexico Health Science Center, Albuquerque, NM, United States
* Corresponding author; email: rdahl{at}salud.unm.edu.
In embryonic stem cells (ESCs), Oct-4 concentration is critical in determining the development of endoderm, mesoderm and trophectoderm. Although Oct-4 expression is essential for mesoderm development, it is unclear if it has a role in the development of specific mesodermal tissues. In this study, we have examined the importance of Oct-4 in the generation of hematopoietic cells by using an inducible Oct-4 ESC line. We demonstrate that Oct-4 has a role in supporting hematopoiesis after specifying brachyury-positive mesoderm. When we suppressed Oct-4 expression before or after mesoderm specification, no hematopoietic cells are detected. However, hematopoiesis can be rescued in the absence of Oct-4 after mesoderm specification if the essential hematopoietic transcription factor SCL is expressed. Our results suggest that for hematopoiesis to occur, Oct-4 is required for the initial specification of mesoderm, and subsequently is required for the development of hematopoietic cells from uncommitted mesoderm.
