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PLoS Genet. 2005 Sep;1(3):e28.

Differential expression of novel potential regulators in hematopoietic stem cells.

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Department of Pathology, Institute of Cancer and Stem Cell Biology and Medicine, Stanford University Medical School, Stanford, California, USA.


The hematopoietic system is an invaluable model both for understanding basic developmental biology and for developing clinically relevant cell therapies. Using highly purified cells and rigorous microarray analysis we have compared the expression pattern of three of the most primitive hematopoietic subpopulations in adult mouse bone marrow: long-term hematopoietic stem cells (HSC), short-term HSC, and multipotent progenitors. All three populations are capable of differentiating into a spectrum of mature blood cells, but differ in their self-renewal and proliferative capacity. We identified numerous novel potential regulators of HSC self-renewal and proliferation that were differentially expressed between these closely related cell populations. Many of the differentially expressed transcripts fit into pathways and protein complexes not previously identified in HSC, providing evidence for new HSC regulatory units. Extending these observations to the protein level, we demonstrate expression of several of the corresponding proteins, which provide novel surface markers for HSC. We discuss the implications of our findings for HSC biology. In particular, our data suggest that cell-cell and cell-matrix interactions are major regulators of long-term HSC, and that HSC themselves play important roles in regulating their immediate microenvironment.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests. As a former advisory board member of Amgen, ILW owns significant Amgen stock. He also cofounded and consulted for Systemix; cofounded Cellerant Therapeutics, a spin-off from Systemix Novartis to transplant human HSC; and is a cofounder and a director of the company Stem Cells, which is involved in the isolation and study of human central nervous system stem cells, liver-repopulating cells, and pancreatic islet/progenitor cells.

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