Transcriptional Characterization of the Notch Signaling Pathway in Rodent Multipotent Adult Progenitor Cells

Melinda HAJDU2, Aernout LUTTUN1, Beatriz PELACHO1, Terry C BURNS1, Lucas CHASE1, María GUTIÉRREZ-PÉREZ3, Yuehua JIANG1, Todd LENVIK1, Virág VAS4, Ferenc UHER4, Anna SEBESTYÉN2, Catherine VERFAILLIE5

1Stem Cell Institute, University of Minnesota Medical School, Minneapolis, USA
21st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
3Hematology and Cell Therapy, Clínica Universitaria, University of Navarra, Pamplona, Spain
4Stem Cell Biology Unit, National Medical Center, Budapest, Hungary
5Stem Cell Institute, Catholic University of Leuven, Leuven, Belgium


The Notch signaling pathway is a multifunctional, evolutionarily conserved pathway, which plays an important role in development as well as stem cell biology. Multipotent adult progenitor cells (MAPCs) represent a unique stem cell population, which is capable of differentiating into cell types of the ectodermal, mesodermal and endodermal lineages in vitro, and contribute to most somatic cell types in vivo. Our aim was to characterize the gene expression of Notch signaling elements in rodent MAPCs. We show that transcripts for Notch-receptors, ligands, regulatory molecules of the pathway and the Hairy/Enhancer of Split-1 (HES-1) target gene are present in mouse and rat low-Oct4 MAPCs. We found that mouse Notch3 and rat Notch1 transcripts increased when cells were cultured at high density for 48 to 96 hours. HES-1 and HES-related transcription factor-1 (HERP-1), transcriptional targets of Notch-signaling, were both elicited by immobilized Delta1 ligand. In addition, mRNA for Notch1 and Notch3 was also induced by Notch-signaling, suggesting the presence of regulatory feedback loops. Slight differences between mouse and rat derived MAPCs suggest that the exact function, transcriptional regulation and the fine-tuning of the signal may be species specific. Taken together, we characterized the gene expression profile of the Notch pathway in rodent low-Oct4-MAPCs, and showed that the pathway is functional and can be modulated. Our results provide an additional tool and a further basis for a better understanding of stem cell biology. Pathology & Oncology Research, Vol 13, Nr 4, 302-310, 2007

Key words: Notch; HES-1; multipotent adult progenitor cell; stem cell

Received: Oct 10, 2007; accepted: Dec 5, 2007
Correspondence: Melinda HAJDU, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllõi út 26. Budapest H-1085, Hungary; Tel: +36-1-2661638 / 4430, Fax: +36-1-3171074; E-mail:

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