Regulation of cell cycle in hematopoietic stem cells by the niche.

The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for cell cycle regulation of HSCs. Monitoring of the quiescence of HSCs using by a new stem cell marker, Side Population (SP), revealed that the cell cycle status of HSCs is dynamically controlled by the microenvironments. We have recently revealed a molecular mechanism in which cell cycle of HSCs is regulated by the niche. HSCs expressing the receptor tyrosine kinase Tie2 are adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 and its ligand Angiopoietin-1 (Ang-1) leads to tight adhesion of HSCs to stromal cells, resulting in maintainance of long-term repopulating activity of HSCs. Thus, Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche. The understanding of cell cycle control in stem cells leads to development of new strategy for progress in regenerative medicine.