Regulation of stem cells in the niche

Stem cells have a self-renewal capacity as well as the capacity to differentiate into single or multiple lineages. In this review, we discuss the mechanism of maintenance of "stemness" in hematopoietic systems and refer to our studies of corneal epithelial stem cells. The quiescent state is believed to be indispensable for the maintenance of hematopoietic stem cells (HSC). Interaction of HSC with their particular microenvironments, known as stem cell niches, is critical for the cell cycle regulation of HSC. Monitoring of the quiescence of HSC by a side population (SP) revealed that the cell cycle status of HSC is dynamically controlled by microenvironments. We recently discovered a molecular mechanism by which the cell cycle of HSC is regulated by the niche. HSC expressing tyrosine kinase Tie2 receptors adhere to osteoblasts in the bone marrow (BM) niche. The interaction of Tie2 and its ligand angiopoietin-1 (Ang-1) leads to tight adhesion of HSC to stromal cells, resulting in the maintenance of long-term repopulating activity of HSC. Thus, the Tie2/Ang-1 signaling pathway plays a critical role in maintaining HSC in the quiescent state in the BM niche. Understanding of the relationships of stem cells to their niches should lead to development of new strategies directed toward regeneration.