Hematopoietic Stem Cells from Embryo to ES Cells

A major stumbling block in translating stem cell therapy to the clinic has been our inability to generate functional adult stem cells from embryonic stem (ES) or induced pluripotent stem (iPS) cells in vitro. Our goal is to better understand the process of HSC formation and maturation in the mouse embryo, and to apply this knowledge towards generating HSCs from ES/iPS cells in vitro. Hematopoietic progenitor and stem cells develop from a small, transient population of endothelial cells in the embryo called “hemogenic endothelium”. Hemogenic endothelium produces both early embryonic blood cell progenitors, and later HSCs. We recently identified a marker specific for the HSC-generating hemogenic endothelium in the embryo. We will attempt to identify a similar HSC-producing hemogenic endothelial population in ES cell cultures. We will examine the relationship between early lymphoid progenitors and HSCs in the embryo, to determine whether lymphoid progenitors are useful surrogates for HSCs in ES/iPS cell cultures. Finally, we will examine the process by which pre-HSCs mature into HSCs, and will try to reproduce this process using ES cells in vitro.

Copyright ©2013 NHLBI Progenitor Cell Biology Consortium.

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