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TISSUE-SPECIFIC STEM CELLS |
1 Department of Biomedical Sciences, Biological Chemistry Section, University of Modena and Reggio Emilia, Via Campi 297, 41100 Modena, Italy
* To whom correspondence should be addressed. E-mail: manfredini.rossella{at}unimore.it.
| Abstract |
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CD34 is a transmembrane protein strongly expressed on hematopoietic stem/progenitor cells (HSCs); despite its importance as a marker of HSCs, its function is still poorly understood, even if a role in cell adhesion has been demonstrated. In order to characterize the function of CD34 antigen on human HSCs, we examined, by both inhibition and over-expression, the role of CD34 in the regulation of HSC lineage differentiation.
Our results demonstrate that CD34 silencing enhances HSC granulocyte and megakaryocyte differentiation and reduces erythroid maturation. In agreement with these results, the gene expression profile of these cells reveals the up-regulation of genes involved in granulocyte and megakaryocyte differentiation and the down-regulation of erythroid genes. Consistently, the retroviral mediated CD34 overexpression leads to a remarkable increase of erythroid progenitors and a dramatic decrease of granulocyte progenitors as evaluated by clonogenic assay.
Altogether these data indicate that CD34 molecule promotes the differentiation of CD34+ hematopoietic progenitors towards the erythroid lineage, that is achieved, at least in part, at the expense of granulocyte and megakaryocyte ones.
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S. Salati and R. Zini contributed equally to this work.
Key Words. CD34 antigen, Hematopoietic Stem Cells, Hematopoietic progenitor cells, Hematopoiesis, Myeloid Differentiation, RNA interference
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