Modeling and Identification of a Gene Regulatory Network Programming Erythropoiesis

摘要

The development of mature blood cells of distinct lineages from the hematopoietic stem cells (hematopoiesis) involves a progressive restriction of differentiation potential and the establishment of lineage-specic gene expression profiles. The establishment of these profiles relies on lineage-specic transcription factors to modulate the expression of their target genes. This work is embedded in a wider ErasmusMC/CWI collaboration that develops the informatics and mathematics to underpin studies on gene expression regulation by mapping and analyzing the regulatory pathways and networks of transcription factors that control cellular functions (so called Gene Regulatory Networks or GRN's). This project is concerned with the mathematical part and concentrates on a GRN central to erythropoiesis. Among the many housekeeping and tissue-specic genes involved in the differentiation and the commitment of hematopoietic stem cells to erythrocytes (erythropoiesis), we focus on a small pool of genes. In depth characterization of the necessary expression patterns and gene regulatory interactions responsible for the the set of commitments all along the erythroid lineage is essential to gain fundamental insight into the behaviour of these complex networks and to design further experiments. Ultimately, this may lead to ways to rescue erythroid differentiation in several anemic diseases.