Hematopoietic fingerprints: an expression database of stem cells and their progeny.
Hematopoietic stem cells (HSCs) continuously regenerate the hematologic system, yet few genes regulating this process have been defined. To identify candidate factors involved in differentiation and self-renewal, we have generated an expression database of hematopoietic stem cells and their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and naive T cells, and B cells. Bioinformatic analysis revealed HSCs were more transcriptionally active than their progeny and shared a common activation mechanism with T cells. Each cell type also displayed unique biases in the regulation of particular genetic pathways, with Wnt signaling particularly enhanced in HSCs. We identified approximately 100-400 genes uniquely expressed in each cell type, termed lineage "fingerprints." In overexpression studies, two of these genes, Zfp 105 from the NK cell lineage, and Ets2 from the monocyte lineage, were able to significantly influence differentiation toward their respective lineages, demonstrating the utility of the fingerprints for identifying genes that regulate differentiation.
Chambers
Stuart M
SM
Interdepartmental Program of Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Boles
Nathan C
NC
Lin
Kuan-Yin K
KY
Tierney
Megan P
MP
Bowman
Teresa V
TV
Bradfute
Steven B
SB
Chen
Alice J
AJ
Merchant
Akil A
AA
Sirin
Olga
O
Weksberg
David C
DC
Merchant
Mehveen G
MG
Fisk
C Joseph
CJ
Shaw
Chad A
CA
Goodell
Margaret A
MA
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; D051153:Wnt Proteins; C118801:Zfp 105 protein, mouse