| The development of B-cells from hematopoietic stem cells is a highly ordered process and is known to be controlled by a complex network of transcription factors. Recent studies revealed that microRNAs (miRNAs), a class of ~22-nucleotide (nt) non-coding RNAs that control gene expression by destabilizing target messenger RNAs or repress protein translation, may play an important role in the orchestration of B-cell development. The proposed study aims to dissect the role of miRNAs in B-cell development. Specifically, I will define miRNA expression at various B-cell developmental stages, investigate the function of miRNAs during B-cell development, and identify the miRNA target genes that are critical to B-cell development. The knowledge yielded by this study can be integrated with the known transcriptional networks that control B-cell development. Furthermore, this study will contribute to the understanding of miRNA-mediated gene regulation and its roles in normal developmental processes in general. Finally, determination of the miRNA expression profiles and their specific functions during B-cell development will provide a solid foundation for future studies regarding the roles of miRNAs in B-cell malignancies, including B-ALL, CLL and B-cell lymphomas that arise during different stages of B-cell development. |
