"Application of Small Molecule CHIR99021 Leads to the Loss of Hemangioblast Progenitor and Increased Hematopoiesis of Human Pluripotent Stem Cells".
Abstract
Improving the understanding of the intricacies of hematopoietic specification of induced or embryonic pluripotent stem cells is beneficial for many areas of research and translational medicine. Currently, it is not clear whether during hPSC hematopoietic differentiation in vitro the maturation of definitive progenitors proceeds through a primitive progenitor (hemangioblast) intermediate or develops independently. The objective of this study is to investigate the early stages of hematopoietic specification of pluripotent stem cells in vitro. By implementing an adherent culture, serum-free differentiation system, which utilizes a small molecule CHIR99021 to induce hPSC toward various hematopoietic lineages, we established that, compared to OP9 co-culture hematopoietic induction system, the application of CHIR99021 alters the early steps of hematopoiesis such as hemangioblast (HB), angiogenic hematopoietic progenitors (AHP) and hemogenic endothelium (HE). Importantly, it is associated with the loss of hemangioblast progenitor, loss of CD43+ (primitive hematopoietic marker) expression, and predominant development of BFU erythroid colonies in semisolid media. These data support the hypothesis that the divergence of primitive and definitive programs during hPSC differentiation precedes the hemangioblast stage. Furthermore, we showed that the inhibition of primitive hematopoiesis is associated with increase in hematopoietic potential, which is a fruitful finding for a growing need of lymphoid and myeloid cells in translational applications.
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