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.
| Original language | English |
|---|---|
| Pages (from-to) | 273-281 |
| Number of pages | 9 |
| Journal | European Journal of Haematology |
| Volume | 77 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 1 2006 |
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All Science Journal Classification (ASJC) codes
- Hematology
Cite this
Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation. / Tachikawa, Yoshimichi; Matsushima, Takamitsu; Abe, Yasunobu; Sakano, Seiji; Yamamoto, Masahiro; Nishimura, Junji; Nawata, Hajime; Takayanagi, Ryouichi; Muta, Koichiro.
In: European Journal of Haematology, Vol. 77, No. 4, 01.10.2006, p. 273-281.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation
AU - Tachikawa, Yoshimichi
AU - Matsushima, Takamitsu
AU - Abe, Yasunobu
AU - Sakano, Seiji
AU - Yamamoto, Masahiro
AU - Nishimura, Junji
AU - Nawata, Hajime
AU - Takayanagi, Ryouichi
AU - Muta, Koichiro
PY - 2006/10/1
Y1 - 2006/10/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33748369677&partnerID=8YFLogxK
U2 - 10.1111/j.0902-4441.2006.t0-1-EJH2708.x
DO - 10.1111/j.0902-4441.2006.t0-1-EJH2708.x
M3 - Article
C2 - 16930143
AN - SCOPUS:33748369677
VL - 77
SP - 273
EP - 281
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 4
ER -