It is a fundamental question regarding how to keep the balance between long term maintenance of stem cells and meanwhile supporting active tissue regeneration. The stem cell niche plays an essential role in maintenance and regulation of stem cells. In mammals, however, keep stem cells as quiescent is an important mechanism for long term maintenance of stem cells. How to fulfill these two tasks simultaneously is a challenge. Here we will discuss our recent concept of separate zones for maintenance and expansion of stem cells in organisms with long life span.