The Notch Delta-4 ligand helps to maintain the quiescence and the short-term reconstitutive potential of haematopoietic progenitor cells through activation of a key gene network.
Stem Cell Res
; 13(3 Pt A): 431-41, 2014 Nov.
Article
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| MEDLINE
| ID: mdl-25460604
ABSTRACT
Understanding the role of Notch and its ligands within the different bone marrow niches could shed light on the mechanisms regulating haematopoietic progenitor cells (HPCs) maintenance and self-renewal. Here, we report that murine bone marrow HPCs activation by the vascular Notch Delta-4 ligand maintains a significant proportion of cells specifically in the G0 state. Furthermore, Delta-4/Notch pathway limits significantly the loss of the in vivo short-term reconstitutive potential upon transplantation of Delta-4 activated HPCs into lethally irradiated recipient mice. Both effects are directly correlated with the decrease of cell cycle genes transcription such as CYCLIN-D1, -D2, and -D3, and the upregulation of stemness related genes transcription such as BMI1, GATA2, HOXB4 and C-MYC. In addition, the transcriptional screening also highlights new downstream post-transcriptional factors, named PUMILIO1 and -2, as part of the stem signature associated with the Delta-4/Notch signalling pathway.
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Banco de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
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Péptidos y Proteínas de Señalización Intracelular
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Receptores Notch
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Stem Cell Res
Año:
2014
Tipo del documento:
Article