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 stemness and how they interact with each other will help us to manipulate these cells more efficiently in the future.


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 19p13.3. 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.


CONCLUSIONS
This study provides the foundation for a more detailed understanding of CD34+ HSPCs.
Chang
Shing-Jyh
SJ
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and National Tsing Hua University, HsinChu, Taiwan.
Huang
Tse-Sung
TS
Wang
Kung-Liahng
KL
Wang
Tao-Yeuan
TY
Yang
Yuh-Cheng
YC
Chang
Margaret Dah-Tsyr
MD
Wu
Yu-Hsuan
YH
Wang
Hsei-Wei
HW
D018952:Antigens, CD34 / Q000032:analysis*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D042783:Endothelial Cells / Q000737:chemistry / Q000648:ultrastructure; D050989:GATA2 Transcription Factor / Q000235:genetics; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000648:ultrastructure; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000648:ultrastructure; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction
D018952:Antigens, CD34; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor