Differential Expression of Novel Potential Regulators in Hematopoietic Stem Cells

Abstract

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.

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes

“…For instance, long-term (LT) repopulating activity of HSCs is contained entirely in the HSC fraction expressing HMGB3, 18 and accordingly, LT-HSCs express higher levels of HMGB3. 19 Also NDN and MLLT3 are upregulated in LT-HSCs. 19 Elimination of reactive oxygen species by catalase (CAT) was recently shown to be required for HSC self-renewal 20 and accordingly, CAT is upregulated in LT-HSCs.…”

Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

“…Endoglin is highly expressed in LT-HSCs at the mRNA and protein levels; in short-term HSCs (ST-HSCs), Endoglin expression levels are about half that of LT-HSCs [27]. CD150 is a member of the SLAM family, whose expression, as for Endoglin, has been associated with LT-HSCs [6,7], although the question of whether all LT-HSCs are CD150 þ remains controversial [28,29]. We analyzed the expression levels of Endoglin and CD150 at the SP SK cell surface.…”

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

“…Indeed, there is evidence that the subsets of short-term and long-term repopulating HSC differ in that respect. 35 Thus, it will be important to define the clonal composition of different populations of HSC that are obtained with different selection methods. Perhaps, a different composition of HSC types in different purified populations could reconcile some of the strikingly discrepant results in HSC research.…”