Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
Department of Medicine
PI: Rita C. Perlingeiro
The Role of Endoglin in Hemangioblast Development
This project aims toward an understanding of the events involved in lineage determination as pluripotent cells commit to hematopoietic and endothelial fates. This knowledge is fundamental to the development of regenerative medicine based on embryonic stem (ES) cells for the treatment of diseases of hematologic and endothelial origin. The current model postulates that the hematopoietic and endothelial lineages arise in mesoderm from a common bipotent progenitor—the hemangioblast. Although an in vitro assay exists for the hemangioblast, very little is known about what enables some mesodermal cells to adopt this fate while others do not, and how the hemangioblast progeny select between endothelial or hematopoietic fates.
In their search for hemangioblast regulatory molecules, these researchers have discovered that endoglin, an ancillary receptor for several members of the TGF-beta superfamily, plays a critical role in hemangioblast specification. Their preliminary studies using ES cells differentiated in vitro demonstrate a profound reduction in hemangioblast frequency in the absence of endoglin. Furthermore, they have shown that endoglin marks the hemangioblast on day 3 of embryoid body differentiation. To date the only cell surface antigen known to mark the hemangioblast is Flk-1.
The researchers’ pilot results point to a role for endoglin in hemangioblast specification as well as provide evidence that endoglin is required for hematopoietic commitment but not endothelial. In this project, they dissect the mechanisms by which endoglin regulates hemangioblast specification and attempt to understand its role in hematopoietic and endothelial commitment.
Liying Zhang, Research Associate