The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar Ilan University, 8 Henrietta Szold, Safed, Israel.
Nat Commun. 2023 Aug 10;14(1):4820. doi: 10.1038/s41467-023-40573-7.
While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment.
虽然细胞分裂对于干细胞和祖细胞的自我更新和分化至关重要，但休眠对于维持干细胞巢的结构和功能也是必需的。在这里，我们利用毛囊来表明，在生长过程中，毛囊的间充质巢，即真皮乳头（DP），通过 DP 中的 Hdac1 和 Hdac2 的活性保持静止，从而抑制细胞周期基因的表达。此外，DP 中的 Hdac1 和 Hdac2 促进 DP 细胞在整个毛发生长周期中的存活。虽然在生长和退化过程中，这包括下调 p53 活性和控制 p53 非依赖性程序，但在静止状态下，这主要涉及 p53 非依赖性机制。值得注意的是，DP 中的 Hdac1 和 Hdac2 在生长阶段也参与协调毛囊周期时钟，通过维持 DP 附近生理水平的 Wnt 信号。我们的发现不仅深入了解了维持干细胞巢在不断变化的微环境中功能的分子机制，而且还揭示了相同的机制提供了一个分子工具箱，使 DP 能够影响和微调微环境。
