Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation

Yoshimichi Tachikawa, Takamitsu Matsushima, Yasunobu Abe, Seiji Sakano, Masahiro Yamamoto, Junji Nishimura, Hajime Nawata, Ryouichi Takayanagi, Koichiro Muta

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish
Pages (from-to)273-281
Number of pages9
JournalEuropean Journal of Haematology
Volume77
Issue number4
DOIs
Publication statusPublished - Oct 1 2006

Fingerprint

Ligands
Notch Receptors
Erythroid Precursor Cells
Erythroid Cells
Hematopoietic Stem Cells
Cell Communication
Real-Time Polymerase Chain Reaction
Cultured Cells
Signal Transduction
Cell Survival
Flow Cytometry
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Tachikawa, Y., Matsushima, T., Abe, Y., Sakano, S., Yamamoto, M., Nishimura, J., ... Muta, K. (2006). Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation. European Journal of Haematology, 77(4), 273-281. https://doi.org/10.1111/j.0902-4441.2006.t0-1-EJH2708.x

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 journalArticle

Tachikawa, Y, Matsushima, T, Abe, Y, Sakano, S, Yamamoto, M, Nishimura, J, Nawata, H, Takayanagi, R & Muta, K 2006, 'Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation', European Journal of Haematology, vol. 77, no. 4, pp. 273-281. https://doi.org/10.1111/j.0902-4441.2006.t0-1-EJH2708.x
Tachikawa, Yoshimichi ; Matsushima, Takamitsu ; Abe, Yasunobu ; Sakano, Seiji ; Yamamoto, Masahiro ; Nishimura, Junji ; Nawata, Hajime ; Takayanagi, Ryouichi ; Muta, Koichiro. / Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation. In: European Journal of Haematology. 2006 ; Vol. 77, No. 4. pp. 273-281.
@article{6684ba0453fb47fbba6d17da0e43e516,
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.",
author = "Yoshimichi Tachikawa and Takamitsu Matsushima and Yasunobu Abe and Seiji Sakano and Masahiro Yamamoto and Junji Nishimura and Hajime Nawata and Ryouichi Takayanagi and Koichiro Muta",
year = "2006",
month = "10",
day = "1",
doi = "10.1111/j.0902-4441.2006.t0-1-EJH2708.x",
language = "English",
volume = "77",
pages = "273--281",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell",
number = "4",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=33748369677&partnerID=8YFLogxK

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 -