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

During ontogeny, the hematopoietic system is established from mesoderm-deri ved precursors; however, molecular events regulating the onset of hematopoi esis 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 acc essory receptor for members of the TGF-beta superfamily. Here it is reporte d that during the differentiation of murine embryonic stem (ES) cells in vi tro, hematopoietic commitment within Flk1(+) mesodermal precursor populatio ns 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 wheth er CD105 plays a functional role during early hematopoietic development, th e potential of CD105-deficient ES cells to differentiate into various hemat o-poietic lineages in vitro was assessed. In the absence of CD105, myelopoi esis and definitive erythropoiesis were severely impaired. In contrast, lym phopoiesis appeared to be only mildly affected. Thus, these findings sugges t that the regulated expression of CD105 functions to support lineage-speci fic hematopoietic development from Flk1(+) precursors. (C) 2001 by The Amer ican Society of Hematology.