title: Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation.
abstract: Notch signaling plays an important role in cell fate decisions in developmental systems. To clarify its role in committed hematopoietic progenitor cells, we investigated the effects of Notch signaling in erythroid colony forming cells (ECFCs) generated from peripheral blood. ECFCs express Notch receptors, Notch1 and Notch2, and Notch ligands Delta1, Delta4, and Jagged1. When we assayed the effects of Notch ligands on erythroid maturation by flow cytometry, we found that immobilized Delta1 and immobilized Delta4 in particular inhibited maturation, whereas Jagged1 had no effect. In addition, Delta4 inhibited proliferation without reducing cell viability. Increases in expression levels of the Notch target gene hairy enhancer of split (HES) -1 were evident by real-time PCR after stimulation with immobilized Delta4. The effect of soluble Delta4 on expression of HES-1 was less pronounced than that seen with the immobilized form, indicating that all surface-bound ligands are important for effective signal transduction. When ECFCs were cultured in the presence of soluble Delta4 at a low cell concentration, erythroid maturation was slightly inhibited, but at a high concentration, maturation was promoted via competition of soluble Delta4 with endogenous ligands. These results indicate a pivotal role of Notch signaling in regulating erythroid maturation and proliferation, and further suggest that cell-cell interactions modulate growth of erythroid progenitor cells via Notch system.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Tachikawa
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Matsushima
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Seiji
authors.initials: S
authors.lastname: Sakano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Muta
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D015672:Erythroid Precursor Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D016895:Culture Media, Serum-Free; D017931:DNA Primers; D051880:Receptors, Notch