Alternative Mechanisms of Gene Regulation During Hematopoiesis

Description

Gene regulation orchestrates the development of different cell types and organs from the same genetic blueprint. While the basic mode of gene regulation is driven by transcription factors, there are a variety of other mechanisms that determine the amount of RNA produced per genes. In this work we first investigate specifically intron retention as a mode of alternative splicing that alters the cellular transcriptomes. As a model, we use hematopoiesis. We compare intron retention in different stages of human and mouse B-cell development to granulocyte differentiation. We further explore expression and binding patterns of splicing regulatory factors. Second, we investigate the role of lncRNAs in the transdifferentiation of B-cell related lymphoma cells to macrophages. We specifically explore the role of a set of upregulated lncRNAs during this process. We deplete their expression during transdifferentiation with CRISPR/Cas9 to identify potential genes that retard or block the process and therefore are crucial for changing cell identity. (Description from external book data)