The article by Linheng Li and Hans Clevers discusses the coexistence of quiescent and active adult stem cells in mammals, challenging the prevailing model that assumes a single quiescent stem cell population. They propose that both quiescent and active stem cell subpopulations may coexist in separate yet adjoining locations within tissues. The authors integrate insights from bone marrow, intestinal epithelium, and hair follicle to support their model. In the hair follicle, quiescent stem cells (label-retaining cells, LRCs) and active stem cells (Lgr5+ cells) are found in adjacent regions. In the intestinal epithelium, quiescent stem cells (LRCs at the +4 position) and active stem cells (Lgr5+ cells at the crypt bottom) are also found in separate zones. In bone marrow, quiescent hematopoietic stem cells (HSCs) and active HSCs are located in different regions, with the quiescent population serving as a backup for the active population. The authors suggest that this zoned model of stem cell populations may provide a robust mechanism for tissue self-renewal and damage repair, ensuring high rates of physiological renewal and flexible repair capabilities.The article by Linheng Li and Hans Clevers discusses the coexistence of quiescent and active adult stem cells in mammals, challenging the prevailing model that assumes a single quiescent stem cell population. They propose that both quiescent and active stem cell subpopulations may coexist in separate yet adjoining locations within tissues. The authors integrate insights from bone marrow, intestinal epithelium, and hair follicle to support their model. In the hair follicle, quiescent stem cells (label-retaining cells, LRCs) and active stem cells (Lgr5+ cells) are found in adjacent regions. In the intestinal epithelium, quiescent stem cells (LRCs at the +4 position) and active stem cells (Lgr5+ cells at the crypt bottom) are also found in separate zones. In bone marrow, quiescent hematopoietic stem cells (HSCs) and active HSCs are located in different regions, with the quiescent population serving as a backup for the active population. The authors suggest that this zoned model of stem cell populations may provide a robust mechanism for tissue self-renewal and damage repair, ensuring high rates of physiological renewal and flexible repair capabilities.