Open AccessThe Kinetic Status of Hematopoietic Stem Cell Subpopulations Underlies a Differential Expression of Genes Involved in Self‐Renewal, Commitment, and Engraftment
Author(s) -
Manfredini Rossella,
Zini Roberta,
Salati Simona,
Siena Michela,
Tenedini Elena,
Tagliafico Enrico,
Montanari Monica,
ZanoccoMarani Tommaso,
Gemelli Claudia,
Vignudelli Tatiana,
Grande Alexis,
Fogli Miriam,
Rossi Lara,
Fagioli Maria Elena,
Catani Lucia,
Lemoli Roberto M.,
Ferrari Sergio
Publication year - 2005
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2004-0265
Subject(s) - biology , haematopoiesis , stem cell , gene , microbiology and biotechnology , hematopoietic stem cell , gene expression , expression (computer science) , genetics , immunology , computer science , programming language
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.