352. CD34+ Hematopoietic Stem-Progenitor Cell MicroRNA Expression and Function: The miR Circuit Diagram of Differentiation Control

Since lin-4, the founding member of the class, was described, microRNAs (miRs) have become a recently realized class of epigenetic elements which modify translation of mRNA to protein, and which also may result in gene silencing through chromatin remodeling. First discovered in C. elegans, miRs have been identified in numerous other organisms including drosophila, rat, mouse, and humans. To date, they have been shown to control cellular metabolism, apoptosis, differentiation and development. Even more importantly aberrant expression of miRs and deletion of miRs are highly associated with the development of various cancers. To better understand the role of miRs in normal hematopoiesis we have determined the microRNA expression profile of primary normal human PBSC and bone marrow CD34+ cells. We have combined this data with the extensive mRNA expression data obtained from CD34+ HSPC, CD34+/CD38-/Lin- HSC-enriched, and CD34+/ CD38+/Lin+ HPC-enriched populations in a previous study. (Cancer Research 64:4344) Combining these two datasets into one integrated database has allowed us to intricately examine the global interaction of HSPC mRNAs and microRNAs, and to also predict which miRs are involved with differentiation of the hematopoietic system. These findings offer promising new targets for the study of stem cell differentiation and targets for genetic therapies of hematopoietic stem cells.