We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways.
- Authors
Huang, Jian; Nguyen-McCarty, Michelle; Hexner, Elizabeth O; Danet-Desnoyers, Gwenn; Klein, Peter S
- Abstract
Hematopoietic stem cell (HSC) self renewal and lineage commitment depend on complex interactions with the microenvironment. The ability to maintain or expand HSCs for clinical applications or basic research has been substantially limited because these interactions are not well defined. Recent evidence suggests that HSCs reside in a low-perfusion, reduced-nutrient niche and that nutrient-sensing pathways contribute to HSC homeostasis. Here we report that suppression of the mTOR pathway, an established nutrient sensor, combined with activation of canonical Wnt-?-catenin signaling, allows for the ex vivo maintenance of human and mouse long-term HSCs under cytokine-free conditions. We also show that the combination of two clinically approved medications that together activate Wnt-?-catenin and inhibit mTOR signaling increases the number (but not the proportion) of long-term HSCs in vivo.
- Subjects
HEMATOPOIETIC stem cells; MTOR protein; HOMEOSTASIS; CATENINS; CELLULAR signal transduction; CYTOKINES
- Publication
Nature Medicine, 2012, Vol 18, Issue 12, p1778
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.2984