Stem cell factor (SCF), the ligand for the c-kit receptor, is essential for the production of red blood cells during development and stress erythropoiesis. SCF promotes erythroblast proliferation and survival, while delaying erythroid differentiation through mechanisms that are largely unknown. In cultures of primary human differentiating erythroblasts, we found that SCF induces an increase in the expression of Notch2, a member of the Notch family implicated in the control of cell growth and differentiation. Functional inhibition of either Notch or its ligand Jagged1 inhibited the effects of SCF on erythroid cell expansion. SCF also induced the expression of Hes-1 and GATA-2, which may contribute to transduce Notch2 signals in response to SCF. Transduction of primary erythroid precursors with a dominant-negative Notch2 mutant inhibited both basal and SCF-mediated erythroblast expansion, and counteracted the effects of SCF on erythroblast differentiation. These findings provide a clue to understand the effects of increased proliferation and delayed differentiation elicited by SCF on the erythroid compartment and indicate Notch2 as a new player in the regulation of red cell differentiation.

The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis / Zeuner, A; Francescangeli, F; Signore, Michele; Venneri, MARY ANNA; Pedini, F; Felli, N; Pagliuca, A; Conticello, C; De Maria, R.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - STAMPA. - 18:2(2011), pp. 371-380. [10.1038/cdd.2010.110]

The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis

SIGNORE, MICHELE;VENNERI, MARY ANNA;
2011

Abstract

Stem cell factor (SCF), the ligand for the c-kit receptor, is essential for the production of red blood cells during development and stress erythropoiesis. SCF promotes erythroblast proliferation and survival, while delaying erythroid differentiation through mechanisms that are largely unknown. In cultures of primary human differentiating erythroblasts, we found that SCF induces an increase in the expression of Notch2, a member of the Notch family implicated in the control of cell growth and differentiation. Functional inhibition of either Notch or its ligand Jagged1 inhibited the effects of SCF on erythroid cell expansion. SCF also induced the expression of Hes-1 and GATA-2, which may contribute to transduce Notch2 signals in response to SCF. Transduction of primary erythroid precursors with a dominant-negative Notch2 mutant inhibited both basal and SCF-mediated erythroblast expansion, and counteracted the effects of SCF on erythroblast differentiation. These findings provide a clue to understand the effects of increased proliferation and delayed differentiation elicited by SCF on the erythroid compartment and indicate Notch2 as a new player in the regulation of red cell differentiation.
01 Pubblicazione su rivista::01a Articolo in rivista
The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis / Zeuner, A; Francescangeli, F; Signore, Michele; Venneri, MARY ANNA; Pedini, F; Felli, N; Pagliuca, A; Conticello, C; De Maria, R.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - STAMPA. - 18:2(2011), pp. 371-380. [10.1038/cdd.2010.110]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/768573
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 21
social impact