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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
- Source :
- Stem Cell Research, Vol 13, Iss 3, Pp 431-441 (2014)
- Publication Year :
- 2014
- Publisher :
- Elsevier, 2014.
-
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.
- Subjects :
- Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 18735061 and 18767753
- Volume :
- 13
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Stem Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.311910aa12e4a058dc38a5cf8cd0803
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.scr.2014.10.002