Stem Cell Research (Nov 2014)

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

  • Cyril Catelain,
  • Fabio Michelet,
  • Aurore Hattabi,
  • Sonia Poirault-Chassac,
  • Thierry Kortulewski,
  • Diana Tronik-Le Roux,
  • William Vainchenker,
  • Evelyne Lauret

DOI
https://doi.org/10.1016/j.scr.2014.10.002
Journal volume & issue
Vol. 13, no. 3
pp. 431 – 441

Abstract

Read online

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.