Increased Levels of NOTCH1, NF-κB, and Other Interconnected Transcription Factors Characterize Primitive Sets of Hematopoietic Stem Cells

Rodrigo Alexandre Panepucci, Lucila Habib B. Oliveira, Dalila Luciola Zanette, Rita de Cassia Viu Carrara, Amélia Goes Araujo, Maristela Delgado Orellana, Patrícia Vianna Bonini de Palma, Camila C.B.O. Menezes, Dimas Tadeu Covas, Marco Antonio Zago
2010 Stem Cells and Development  
As previously shown, higher levels of NOTCH1 and increased NF-κB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this fi nding. The CD133 marker defi nes a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics
more » ... ve characteristics of UCB and CD133+ HSC, immunomagnetically purifi ed human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a signifi cantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a signifi cantly higher frequency (than expected by chance) of NF-κB-binding sites (BS), including potentially novel NF-κB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all signifi cantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-κB, and other important TFs on more primitive HSC sets.
doi:10.1089/scd.2008.0397 pmid:19686049 fatcat:w4wt6vcvmrdfhe5cux7hdppuaa