GENETIC NETWORK ANALYSIS OF HUMAN CD34+ HEMATOPOIETIC STEM/PRECURSOR CELLS

Objective: Somatic CD34(+) hematopoietic stem/precursor cells (HSPCs) give rise to hematopoietic cells and endothelial cells and have been used in clinical applications. Understanding the genes responsible for sternness and how they interact with each other will help us to manipulate these cells more efficiently in the future. Materials and Methods: We performed microarray analysis on human CD34(+) HSPCs and on two different progeny cell types, i.e. microvascular endothelial cells and peripheral blood mononuclear cells. Systems biology and advanced bioinformatics tools were used to help clarify the genetic networks associated with these stem cell genes. Results: We identified CD34(+) HSPC genes and found that they were involved in critical biologic processes such as cell cycle regulation, chromosome organization, and DNA repair. We also identified a novel precursor gene cluster on chromosome I 9p13.3. Analysis of HSPC-enriched genes using systems biology tools revealed a complex genetic network functioning in CD34(+) cells, in which several genes acted as hubs to maintain the stability (such as GATA1) or connectivity (such as hepatic growth factor) of the whole network. Conclusion: This study provides the foundation for a more detailed understanding of CD34(+) HSPCs. [Taiwan J Obstet Gynecol 2008;47(4):422-430]