Higher expression of transcription targets and components of the nuclear factor-kappaB pathway is a distinctive feature of umbilical cord blood CD34+ precursors.
Delayed engraftment, better reconstitution of progenitors, higher thymic function, and a lower incidence of the graft-versus-host disease are characteristics associated with umbilical cord blood (UCB) transplants, compared with bone marrow (BM). To understand the molecular mechanisms causing these intrinsic differences, we analyzed the differentially expressed genes between BM and UCB hematopoietic stem and progenitor cells (HSPCs). The expressions of approximately 10,000 genes were compared by serial analysis of gene expression of magnetically sorted CD34(+) cells from BM and UCB. Differential expression of selected genes was evaluated by real-time polymerase chain reaction on additional CD34(+) samples from BM (n = 22), UCB (n = 9), and granulocyte colony stimulating factor-mobilized peripheral blood (n = 6). The overrepresentation of nuclear factor-kappaB (NF-kappaB) pathway components and targets was found to be a major characteristic of UCB HSPCs. Additional promoter analysis of 41 UCB-overrepresented genes revealed a significantly higher number of NF-kappaB cis-regulatory elements (present in 22 genes) than would be expected by chance. Our results point to an important role of the NF-kappaB pathway on the molecular and functional differences observed between BM and UCB HSPCs. Our study forms the basis for future studies and potentially for new strategies to stem cell graft manipulation, by specific NF-kappaB pathway modulation on stem cells, prior to transplant.
Panepucci
Rodrigo Alexandre
RA
Center for Cell Therapy and Regional Blood Center, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Calado
Rodrigo Tocantins
RT
Rocha
Vanderson
V
Proto-Siqueira
Rodrigo
R
Silva
Wilson Araujo
WA
Zago
Marco Antonio
MA
D000328:Adult; D018952:Antigens, CD34 / Q000502:physiology*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D017931:DNA Primers; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D016328:NF-kappa B / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014158:Transcription, Genetic
D018952:Antigens, CD34; D017931:DNA Primers; D016328:NF-kappa B