TY - JOUR
T1 - The kinetic status of hematopoietic stem cell subpopulations underlies a differential expression of genes involved in self-renewal, commitment, and engraftment
AU - Manfredini, Rossella
AU - Zini, Roberta
AU - Salati, Simona
AU - Siena, Michela
AU - Tenedini, Elena
AU - Tagliafico, Enrico
AU - Montanari, Monica
AU - Zanocco-Marani, Tommaso
AU - Gemelli, Claudia
AU - Vignudelli, Tatiana
AU - Grande, Alexis
AU - Fogli, Miriam
AU - Rossi, Lara
AU - Fagioli, Maria Elena
AU - Catani, Lucia
AU - Lemoli, Roberto M.
AU - Ferrari, Sergio
PY - 2005/4
Y1 - 2005/4
N2 - The gene expression profile of CD34- hematopoietic stem cells (HSCs) and the correlations with their biological properties are still poorly understood. To address this issue, we used the DNA microarray technology to compare the expression profiles of different peripheral blood hemopoietic stem/progenitor cell subsets, lineage-negative (Lin-) CD34 -, Lin-CD34+, and Lin+CD34 + cells. The analysis of gene categories differentially expressed shows that the expression of CD34 is associated with cell cycle entry and metabolic activation, such as DNA, RNA, and protein synthesis. Moreover, the significant upregulation in CD34- cells of pathways inhibiting HSC proliferation induces a strong differential expression of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, and growth-arrest genes. According to the expression of their receptors and transducers, interleukin (IL)-10 and IL-17 showed an inhibitory effect on the clonogenic activity of CD34- cells. Conversely, CD34+ cells were sensitive to the mitogenic stimulus of thrombopoietin. Furthermore, CD34- cells express preferentially genes related to neural, epithelial, and muscle differentiation. The analysis of transcription factor expression shows that the CD34 induction results in the upregulation of genes related to self-renewal and lineage commitment. The preferential expression in CD34+ cells of genes supporting the HSC mobilization and homing to the bone marrow, such as chemokine receptors and integrins, gives the molecular basis for the higher engraftment capacity of CD34+ cells. Thus, the different kinetic status of CD34- and CD34+ cells, detailed by molecular and functional analysis, significantly influences their biological behavior.
AB - The gene expression profile of CD34- hematopoietic stem cells (HSCs) and the correlations with their biological properties are still poorly understood. To address this issue, we used the DNA microarray technology to compare the expression profiles of different peripheral blood hemopoietic stem/progenitor cell subsets, lineage-negative (Lin-) CD34 -, Lin-CD34+, and Lin+CD34 + cells. The analysis of gene categories differentially expressed shows that the expression of CD34 is associated with cell cycle entry and metabolic activation, such as DNA, RNA, and protein synthesis. Moreover, the significant upregulation in CD34- cells of pathways inhibiting HSC proliferation induces a strong differential expression of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, and growth-arrest genes. According to the expression of their receptors and transducers, interleukin (IL)-10 and IL-17 showed an inhibitory effect on the clonogenic activity of CD34- cells. Conversely, CD34+ cells were sensitive to the mitogenic stimulus of thrombopoietin. Furthermore, CD34- cells express preferentially genes related to neural, epithelial, and muscle differentiation. The analysis of transcription factor expression shows that the CD34 induction results in the upregulation of genes related to self-renewal and lineage commitment. The preferential expression in CD34+ cells of genes supporting the HSC mobilization and homing to the bone marrow, such as chemokine receptors and integrins, gives the molecular basis for the higher engraftment capacity of CD34+ cells. Thus, the different kinetic status of CD34- and CD34+ cells, detailed by molecular and functional analysis, significantly influences their biological behavior.
KW - CD34 stem cells
KW - CD34
KW - Differentiation
KW - Engraftment
KW - Hematopoietic stem cells
KW - Microarray Proliferation
KW - Self-renewal
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UR - http://www.scopus.com/inward/citedby.url?scp=20144387852&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2004-0265
DO - 10.1634/stemcells.2004-0265
M3 - Article
C2 - 15790771
AN - SCOPUS:20144387852
VL - 23
SP - 496
EP - 506
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 4
ER -