Higher Expression of Transcription Targets and Components of the NF-B Pathway is a Distinctive Features of Umbilical Cord Blood CD34⁺ Precursors

¹ Center for Cell Therapy and Regional Blood Center, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil
² Bone Marrow Transplantation Unit, Hôpital Saint-Louis, Paris, France

^* To whom correspondence should be addressed. E-mail: marazago{at}usp.br.

	Abstract

Delayed engraftment, better reconstitution of progenitors, higher thymic function, and a lower incidence of the graft versus host disease (GVHD) are characteristics associated with umbilical cord blood (UCB) transplants, when compared to bone marrow (BM). To understand the molecular mechanisms causing these intrinsic differences we analyzed the differentially expressed genes between BM and UCB HSPC. The expression of approximately 10.000 genes were compared by serial analysis of gene expression (SAGE) of magnetically sorted CD34⁺ cells from BM and UCB. Differential expression of selected genes was evaluated by real-time PCR on additional CD34⁺ samples from BM (n=22), UCB (n=9) and G-CSF mobilized peripheral blood (MPB, n=6). The overrepresentation of NF-B pathway components and targets was found to be a major characteristic of UCB HSPC. Additional promoter analysis of 41 UCB overrepresented genes revealed a significantly higher number of NF-B cis-regulatory elements (present in 22 genes), than expected by chance. Our results point to an important role of the NF-B pathway on the molecular and functional differences observed between BM and UCB HSPC. Our study sets the basis for future studies and to potentially new strategies to stem cell graft manipulation, by specific NF-B pathway modulation on stem cells, prior to transplant.

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