The kinetic status of hematopoietic stem cell subpopulations underlies a differential expression of genes involved in self-renewal, commitment, and engraftment.
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.
Manfredini
Rossella
R
Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy.
Zini
Roberta
R
Salati
Simona
S
Siena
Michela
M
Tenedini
Elena
E
Tagliafico
Enrico
E
Montanari
Monica
M
Zanocco-Marani
Tommaso
T
Gemelli
Claudia
C
Vignudelli
Tatiana
T
Grande
Alexis
A
Fogli
Miriam
M
Rossi
Lara
L
Fagioli
Maria Elena
ME
Catani
Lucia
L
Lemoli
Roberto M
RM
Ferrari
Sergio
S
D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D016000:Cluster Analysis; D046508:Culture Techniques; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013926:Thrombopoietin / Q000378:metabolism
D018952:Antigens, CD34; D015415:Biomarkers; D016213:Cyclins; D013926:Thrombopoietin; D018844:Cyclin-Dependent Kinases