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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: Delta - 4/Notch pathway retains the HPCs potential

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 Delta4 ligand maintains a significant proportion of cells specifically in the G0 state. Furthermore, Delta4/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 Delta4/Notch signalling pathway.
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https://www.hal.inserm.fr/inserm-01076086
Contributor : Mireille Bos <>
Submitted on : Tuesday, October 21, 2014 - 10:07:56 AM
Last modification on : Thursday, September 17, 2020 - 3:22:56 AM
Long-term archiving on: : Friday, April 14, 2017 - 1:18:29 PM

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Cyril Catelain, Fabio Michelet, Aurore Hattabi, Sonia Poirault-Chassac, Thierry Kortulewski, et al.. 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: Delta - 4/Notch pathway retains the HPCs potential. Stem cell research, Elsevier, 2014, pp.1-14. ⟨10.1016/j.scr.2014.10.002⟩. ⟨inserm-01076086⟩

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