Blood regeneration: de novo development of human hematopoietic stem cells
|Title||Blood regeneration: de novo development of human hematopoietic stem cells|
|Sponsor||European Research Council - Advanced Grant (ERC-AdG)|
|Institution||College of Medicine and Veterinary Medicine|
Associated cell lines
The objective of this project is to reveal functionally validated intrinsic and extrinsic factors that direct the generation of human hematopoietic stem cells (HSC). Prior knowledge from our own genetic and imaging studies in the mouse embryo show that HSCs are derived from specialized vascular endothelial cells. This, together with the growing body of knowledge in the literature on reprogramming of somatic cells, will be applied to next generation sequencing efforts to identify key genetic modulators that will be implemented in multi-color genetic marking of somatic cells to reveal endothelial to HSC transition (EHT) in novel three dimensional culture systems. Studies will make use of mouse models and be extended to human pluripotent stem cells (hESC and hiPSC) to obtain de novo generated (robust, transplantable) HSCs. These approaches will inform novel strategies to generate human HSCs that will have impact on our understanding of hematopoietic malignancy and/or disease progression and aging, and lead the way for enhanced clinical hematologic therapies.