Our long-term research goals are to understand the mechanisms that regulate stem cell fate decisions. Here, we propose to pursue questions in fetal hematopoiesis by investigating the role, regulation and specification of a novel population of hematopoietic stem cells (HSC). Although this population fulfills the most stringent criteria fo functional HSC, their life-span during normal development is restricted to a limited developmental window. A functional HSC that does not persist into adulthood has never been observed before and therefore defines a novel wave of definitive hematopoiesis with a distinct endpoint. Our discovery of these novel HSC provides a unique opportunity to pursue the mechanisms that regulate the persistence of stem cells throughout life. In addition, the existence of stage-specific HSC will provide insights to how specialized immune cells are established during specific developmental time points to meet the varying demands on the immune system. Because our finding is based on an irreversible genetic deletion event, our model is also uniquely suited for understanding the relationship between cell populations during HSC specification and differentiation during development. These questions will be pursued by a combination of transplantation assays and in vitro experiments. The outcomes will provide essential new insights on the establishment of the blood and immune system guide strategies for combatting developmental hematopoietic disorders, including certain types of anemia, autoimmune disease, and childhood cancer. .

Public Health Relevance

This proposal will investigate the mechanisms regulating the function of blood-forming stem cells during fetal development. The findings will be used to improve the treatment of cancer and disorders of the blood and immune system.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DK100917-02
Application #
8733686
Study Section
Molecular and Cellular Hematology (MCH)
Program Officer
Bishop, Terry Rogers
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Santa Cruz
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064