Role of reactive oxygen species as signal molecules in the pre-commitment phase of adult stem cells.

This mini-review summarizes evidence, provided by our group, relevant to the understanding of how redox signalling may control the fate of adult hematopoietic stem/progenitor cells (HSPCs). In particular it is shown that bone marrow-derived human HSPC are endowed with a composite panel of constitutively active NADPH-oxidases (NOXs) comprising the cell membrane-localized catalytic subunits of the NOX1, NOX2 and NOX4 isoforms. It is proposed that the coordinated activity of the NOX isoforms in HSPCs function as environmental oxygen sensor and generate low level of ROS, which likely serve as second messengers. The pro-oxidant setting, entering into play when HSPCs leave the hypoxic bone marrow niche, would enable them to be more responsive to proliferative/differentiative stimuli. Moreover it is suggested that enhanced ROS elicit mitochondrial "differentiation" in a pre-commitment phase needed to match the bioenergetic request in the oncoming proliferation/differentiation process.