Christopher Sturgeon, PhD

The directed differentiation of human pluripotent stem cells (hPSC) towards the hematopoietic lineages would be an invaluable tool for regenerative medicine, providing cells for both transplantation and in vitro analysis. As the PSC system has been shown to recapitulate developmental events in vitro, it is also a powerful model system for developmental biology, being the only method to-date that allows interrogation of the cellular and molecular mechanisms that regulate human development. Furthermore, the recent technological advancement to generate induced pluripotent stem cells offers the potential to model not only development, but also disease in a dish.

Current efforts to generate an hPSC-derived hematopoietic stem cell (HSC) are plagued by an inability to accurately discriminate between progenitors of the primitive and definitive hematopoietic programs, as there is no anatomical separation between the two in vitro. Briefly, very early in embryonic development the primitive hematopoietic program gives rise to a subset of lineages, including unique erythroblasts with high oxygen-affinity hemoglobin to promote embryonic survival, but no T cells or hematopoietic stem cells. This program is transient, and is shut down prior to the intra-embryonic emergence of the definitive hematopoietic program, which generates the full spectrum of hematopoietic lineages, including T cells and the hematopoietic stem cell. Both programs appear to progress in a similar fashion, passing through a mesodermal precursor and then subsequent hemogenic endothelium. However, as only the definitive program gives rise to a bona fide HSC, understanding the mechanism(s) that control specification of this program are essential to achieving this goal.

The focus of my lab is to elucidate the signaling pathways governing the specification of both hematopoietic programs using hPSC directed differentiation. Through this we aim to better understand the transcriptional and epigenetic regulation that controls HSC development, and identify method(s) to specify a transplantable HSC in the dish. Work in my laboratory is focused on three main objectives:

Understanding human primitive and definitive hematopoietic development

Understanding the endothelial-to-hematopoietic transition in hemogenic endothelium, ultimately giving rise to an HSC

Modeling hematopoietic disease with iPSC

Please visit www.sturgeonlab.com for more information