Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Nature. 2012 Jul 26;487(7408):496-9. doi: 10.1038/nature11218.
Tissue development and regeneration depend on cell-cell interactions and signals that target stem cells and their immediate progeny. However, the cellular behaviours that lead to a properly regenerated tissue are not well understood. Using a new, non-invasive, intravital two-photon imaging approach we study physiological hair-follicle regeneration over time in live mice. By these means we have monitored the behaviour of epithelial stem cells and their progeny during physiological hair regeneration and addressed how the mesenchyme influences their behaviour. Consistent with earlier studies, stem cells are quiescent during the initial stages of hair regeneration, whereas the progeny are more actively dividing. Moreover, stem cell progeny divisions are spatially organized within follicles. In addition to cell divisions, coordinated cell movements of the progeny allow the rapid expansion of the hair follicle. Finally, we show the requirement of the mesenchyme for hair regeneration through targeted cell ablation and long-term tracking of live hair follicles. Thus, we have established an in vivo approach that has led to the direct observation of cellular mechanisms of growth regulation within the hair follicle and that has enabled us to precisely investigate functional requirements of hair-follicle components during the process of physiological regeneration.
组织发育和再生依赖于细胞间相互作用和信号，这些信号靶向干细胞及其直接后代。然而，导致组织正常再生的细胞行为尚不清楚。我们使用一种新的、非侵入性的、双光子活体成像方法，在活体小鼠中随时间研究生理性毛囊再生。通过这些方法，我们监测了上皮干细胞及其后代在生理性毛发生长过程中的行为，以及间充质如何影响它们的行为。与早期研究一致，干细胞在毛发生长的初始阶段处于静止状态，而其后代则更活跃地分裂。此外，干细胞后代的分裂在毛囊内是空间组织的。除了细胞分裂，后代的协调细胞运动允许毛囊的快速扩张。最后，我们通过靶向细胞消融和活体毛囊的长期跟踪，显示了间充质对毛发生长的要求。因此，我们建立了一种体内方法，可以直接观察毛囊内生长调节的细胞机制，并使我们能够在生理性再生过程中精确研究毛囊成分的功能要求。
