Deciphering single-cell niche composition and their effect on hair follicle and dermal papillae Stem Cells regulation during the hair regeneration cycle.

There is a great interest in understanding basic processes that allow the regeneration of tissues in the human body. Most of the organs in mammalian organisms, including humans, must be supported to maintain their function by the existence of a vital pool of multipotent cells called adult stem cells (SCs), which are essential not only for physiological tissue renewal but also to regenerate tissues after injury. Thus, understanding adult SCs regulators that tightly govern the tricky balance of signaling pathways that either activate or inhibit SCs stability is an important question in basic biology and regenerative medicine. Recently, my laboratory discovered the intrinsic molecular mechanism of a competitive balance of BMP/WNT signaling as the fundamental axis to regulate hair follicle Stem Cells (HFSCs) rest and stimulation. However, there is a gap in our scientific knowledge regarding how BMP/WNT signaling integrates the regulation of different molecular networks between hair Stem Cells and different surrounding compartments called niche environments during hair rest and regeneration. Based on that discovery, we proposed a model in which hair Stem Cells coalesce their intrinsic and extrinsic mechanisms with neighboring niche cells, resulting in the preservation of their stemness and hair regenerative potential during an organism’s lifespan. Primarily, in this proposal, we focus on the question of how the intrinsic fluctuation of gene networks in hair Stem Cells affects the surrounding niche environment for proper hair regeneration.