Journal of Blood Disorders & Transfusion

Changes in hematopoietic stem cell behavior as a consequence of sclerostin-deficiency in the bone

2^nd International Conference on Hematology & Blood Disorders

September 29-October 01, 2014 DoubleTree by Hilton Baltimore-BWI Airport, USA

Jennifer O Manilay

Accepted Abstracts: J Blood Disorders Transf

Abstract:

The interactions between diverse cell types within the bone have become an intense research focus, with clinical applications to prevent age‐related bone loss and immune deficiency, and control bone and blood disorders in cancers such as multiple myeloma. Crosstalk between cells of the bone microenvironment and hematopoietic cells affects each other?s behavior, but a significant knowledge gap exists in the basic biology of how these interactions affect hematopoietic stem cell (HSC) maintenance, differentiation, and immunity long‐term. We identified sclerostin, a Wnt signaling antagonist, as a mediator of cell communication between the skeletal and immune systems. Sclerostin‐knockout (KO) mice have higher‐than‐normal bone densities due to dysregulated bone growth. As a consequence, the bone marrow (BM) cavities of KO mice are altered, and we discovered that lack of sclerostin adversely affects B cell development in the BM in a non‐cell autonomous fashion (including deficiencies in the expression of B cell growth factors, such as stem cell factor and CXCL12). These growth factors are also important for HSC maintenance; however, the role of sclerostin in the regulation of HSC function remains an open question. We used HSC exhaustion assays and serial hematopoietic transplantation to study whether sclerostin-deficiency could lead to HSC depletion and hematopoietic failure. Our preliminary results suggest that sclerostin is dispensable for HSC cycle regulation but that its absence affects HSC expansion and differentiation due to changes in the BM supportive niches. These studies have significant implications on the understanding of natural age-related changes in HSC maintenance and immunity.

Biography :

Jennifer O Manilay is an Associate Professor and Founding Faculty Member of the University of California, Merced, and has dedicated her career to understanding the mechanisms that underlie hematopoietic cell development. She completed her PhD in Immunology at Harvard Medical School and Postdoctoral studies at the University of California, Berkeley. Her publications in Journal of Immunology, Experimental Hematology, and Journal of Bone and Mineral Research have been acclaimed by the academic community. One of her short-term goals is to become recognized in the emerging field of ?osteoimmunology?, which explores the molecular and cellular interactions between the skeletal and immune systems.