NRF2 Activation Impairs Quiescence and Bone Marrow Reconstitution Capacity of Hematopoietic Stem Cells.

ABSTRACT: Tissue stem cells are maintained in quiescence under physiological conditions but proliferate and differentiate to replenish mature cells under stressed conditions. The KEAP1-NRF2 system plays an essential role in stress response and cytoprotection against redox disturbance. To clarify the role of the KEAP1-NRF2 system in tissue stem cells, we focused on hematopoiesis in this study and used Keap1-deficient mice to examine the effects of persistent activation of NRF2 on long-term hematopoietic stem cells (LT-HSCs). We found that persistent activation of NRF2 due to Keap1 deficiency did not change the number of LT-HSCs but reduced their quiescence in steady-state hematopoiesis. During hematopoietic regeneration after bone marrow (BM) transplantation, persistent activation of NR

SUBMITTER: Murakami S 

PROVIDER: S-EPMC5599717 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature