Hdac1 and Hdac2 regulate the quiescent state and survival of hair-follicle mesenchymal niche

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. To determine whether Hdac1 and Hdac2 play a role in the DP in regulating the hair cycle, Hdac1 and Hdac2 were ablated specifically in the DP postnatally. Then we preformed gene expression profiling analysis using data obtained from RNA-seq of Control and Hdac1/Hdac2 double mutant at 4 time point (P20, P24, P28 and P60).