Expression and function of CD105 during the onset of hematopoiesis from Flk1+ precursors

During ontogeny, the hematopoietic system is established from mesoderm-derived precursors; however, molecular events regulating the onset of hematopoiesis are not well characterized. Several members of the transforming growth factor beta (TGF-beta) superfamily have been implicated as playing a role during mesoderm specification and hematopoiesis. CD105 (endoglin) is an accessory receptor for members of the TGF-beta superfamily. Here it is reported that during the differentiation of murine embryonic stem (ES) cells in vitro, hematopoietic commitment within Flk1(+) mesodermal precursor populations is characterized by CD105 expression. In particular, CD105 is expressed during the progression from the Flk1(+)CD45(-) to Flk1(-)CD45(+) stage. The developmentally regulated expression of CD105 suggests that it may play a role during early hematopoiesis from Flk1(+) precursors. To determine whether CD105 plays a functional role during early hematopoietic development, the potential of CD105-deficient ES cells to differentiate into various hemato-poietic lineages in vitro was assessed. In the absence of CD105, myelopoiesis and definitive erythropoiesis were severely impaired. In contrast, lymphopoiesis appeared to be only mildly affected. Thus, these findings suggest that the regulated expression of CD105 functions to support lineage-specific hematopoietic development from Flk1(+) precursors. (C) 2001 by The American Society of Hematology.