Endoglin is not Critical for Hematopoietic Stem Cell Engraftment and Reconstitution, but Regulates Adult Erythroid Development

¹ Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and The Lund, Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, Lund, Sweden.
² Immunology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

^* To whom correspondence should be addressed. E-mail: Stefan.Karlsson{at}med.lu.se.

	Abstract

Endoglin is a TGF- accessory receptor recently identified as being highly expressed on long-term repopulating hematopoietic stem cells (HSC). However, little is known regarding its function in these cells. We have employed two complimentary approaches towards understanding endoglin's role in HSC biology; one that efficiently knocks down expression via lentiviral driven shRNA, and another utilizing retroviral mediated over-expression. Altering endoglin expression had functional consequences for hematopoietic progenitors in vitro such that endoglin-suppressed myeloid progenitors (CFU-GM) displayed a higher degree of sensitivity to TGF- mediated growth inhibition, while endoglin over-expressing cells were partially resistant. However, transplantation of transduced bone marrow enriched in primitive hematopoietic stem and progenitor cells revealed that neither endoglin suppression nor endoglin over-expression affected the ability of stem cells to short-term or long-term repopulate recipient marrow. Furthermore, transplantation of cells altered in endoglin expression yielded normal white blood cell proportions and peripheral blood platelets. Interestingly, decreasing endoglin expression increased the clonogenic capacity of early BFU-e erythroid progenitors, while over-expression compromised erythroid differentiation at the basophilic erythroblast phase, suggesting a pivotal role for endoglin at key stages of adult erythropoietic development.