The Regulation of Hematopoietic Stem Cell Function by Granulocyte-Colony Stimulating Factor

Background
Hematopoietic stem cells (HSCs) are a rare population of bone marrow cells that have the capacity to self-renew- to make more stem cells - as well as the ability to generate all of the types of blood cells found in the circulation. Our data show that granulocyte-colony stimulating factor (G-CSF), a naturally-occurring mediator of inflammation and an agent commonly used clinically to harvest HSCs for bone marrow transplantation, impairs HSC function. Specifically, HSCs from G-CSF-treated mice divide less frequently than HSCs from untreated mice, and have a reduced ability to repopulate the blood cells in transplanted mice.

We have also found that HSCs from G-CSF treated mice have increased levels of toll-like receptor (TLR) activity. TLRs are important for recognizing cellular damage and infection, and can influence the capacity of HSCs to divide and generate different types of blood cells.

Project Goal
The proposed experiments aim to understand how increased levels of TLRs on G-CSF- treated HSCs contribute to changes in HSC function. As G-CSF treated HSCs are used in bone marrow transplants in children with cancer, an understanding of the effects of G-CSF on HSCs is critical to the development of improved strategies for harvesting HSCs for transplant.