(From Parent Grant R35HL150826: Stem cells replenish tissues and organs over an organism?s lifetime and can repair damage after injury. With their special capacities for self-renewal and differentiation, stem cells promise to revolutionize medicine. To develop better and safer stem cell therapies, it is critically important to improve the understanding of stem cell regulation. Most of the knowledge about stem cell regulation comes from studies that investigate the aggregate behaviors of thousands to millions of stem cells. However, recent studies suggest that individual hematopoietic stem cells (HSCs) behave substantially differently from one another in both mice and humans. These newly discovered inter-cellular differences present exciting new opportunities for studying HSC regulation. However, they also present significant technical challenges that are difficult to address with conventional approaches. The proposed research program will use a novel systems biology approach combined with quantitative single-cell analysis to determine the cellular and molecular mechanisms underlying HSC heterogeneity and coordination, as well as their influences on aging and the pathogenesis of hematopoietic diseases. Many hematopoietic diseases?such as bone marrow failure, myeloproliferative disorders, myelodysplastic syndromes and other age-associated hematopoietic problems?are initiated by rare cells. The proposed research program will map the precise pathogenesis of these diseases and identify disease founder clones and genes using newly developed single cell tracking and molecular profiling technologies. With these technical advances, the proposed research will also produce new fundamental knowledge about blood regeneration, the foundation of bone marrow transplantation. The long-term objective is to apply the knowledge obtained from the proposed basic research to control blood regeneration for therapeutic use, to detect leukemia and other clonal diseases at early stages, and to effectively treat diseases with advanced stem cell therapies.

Public Health Relevance

(From Parent Grant R35HL150826): The proposed research can help improve the diagnosis and treatment of hematopoietic diseases, particularly the blood and immune diseases associated with aging and TET2 mutations. It can also help improve bone marrow transplantation and develop new blood regeneration treatments that are independent of transplantation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
3R35HL150826-01S1
Application #
10149578
Study Section
Program Officer
Bai, C Brian
Project Start
2020-09-23
Project End
2023-07-31
Budget Start
2020-09-23
Budget End
2021-07-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Southern California
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089