Right ventricular hypertrophy, lung endothelial cell injury, and in situ thrombi are common pathologic characteristics of patients with PAH. Increased numbers of BM-derived CD133⁺ stem cells are found in PAH pulmonary artery wall, but the lineage differentiation of these cells and whether they contribute to the vascular remodeling or play a reparative role are unknown. Increased expression of the myeloid transcription factor GATA-1 is found in PAH CD133⁺ hematopoietic stem cells (HSC) and common myeloid progenitors (CMP), which skew differentiation of PAH CD133⁺ cells into megakaryocyte-erythroid progenitors (MEP). Subsequently, EKLF expression in MEPs induces erythroid commitment, resulting in higher numbers of myeloerythroid progenitors in PAH BM. Engraftment of PAH CD133⁺ HSCs into NOD-SCID mice confirms the increased myeloerythroid proliferation. In analogy to human PAH, xenografted mice develop lung endothelial cell injury, in situ thrombi, and right ventricular hypertrophy. The data reveal a contributory role of BM CD133⁺ myeloid-erythroid progenitors in PAH. Illustration is reprinted with permission of the Cleveland Clinic Center for Medical Art & Photography (copyright 2012; all rights reserved).