Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells

• DOI: 10.1073/pnas.1211175109
• Publication Date: 2012-10-09T04:26:58Z
• Authors: Stella T. Chou; Marta Byrska-Bishop; Joanna M. Tober; Yu Yao; Daniel VanDorn; Joanna B. Opalinska; Jason A. Mills; John Kim Choi; Nancy A. Speck; Paul Gadue; Ross C. Hardison; Richard L. Nemiroff; Deborah L. French; Mitchell J. Weiss
• Keywords: Trisomy; Myelopoiesis

Patients with Down syndrome (trisomy 21, T21) have hematologic abnormalities throughout life. Newborns frequently exhibit abnormal blood counts and a clonal preleukemia. Human T21 fetal livers contain expanded erythro-megakaryocytic precursors enhanced proliferative capacity. The impact of on the earliest stages embryonic hematopoiesis is unknown nearly impossible to examine in human subjects. We modeled yolk sac using induced pluripotent stem cells (iPSCs). Blood progenitor populations generated from iPSCs were present at normal frequency proliferated normally. However, their developmental potential was altered erythropoiesis reduced myelopoiesis, but megakaryocyte production. These overlap those livers, also reflect important differences. Our studies show that confers distinct stage- species-specific hematopoietic defects. More generally, we illustrate how can provide insight into early pathological development.