Ichijo Ryo, Kabata Mio, Kidoya Hiroyasu, Muramatsu Fumitaka, Ishibashi Riki, Abe Kota, Tsutsui Ko, Kubo Hirokazu, Iizuka Yui, Kitano Satsuki, Miyachi Hitoshi, Kubota Yoshiaki, Fujiwara Hironobu, Sada Aiko, Yamamoto Takuya, Toyoshima Fumiko
Department of Biosystems Science, Institute for Frontier Life and Medical Science, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Sci Adv. 2021 Feb 10;7(7). doi: 10.1126/sciadv.abd2575. Print 2021 Feb.
Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3-basal cells (Tbx3-BCs) and their neighboring cells where Adam8-extracellular signal-regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin.
干细胞（SC）的增殖和分化维持着组织的稳态。然而，SCs如何在动态器官中调节协调组织大小仍不清楚。在这里，我们阐述了动态皮肤中的SC调控机制。我们发现，在怀孕小鼠不断扩张的腹部表皮和增殖的足底表皮中，毛囊间表皮干细胞（IFESCs）塑造了基底表皮增殖簇（EPCs）。EPCs由IFESC衍生的Tbx3基底细胞（Tbx3-BCs）及其相邻细胞组成，在这些相邻细胞中，Adam8-细胞外信号调节激酶信号被激活。克隆谱系追踪显示，Tbx3-BC克隆在孕期出现在腹部表皮，产后分化。在足底表皮中，Tbx3-BCs作为长寿SCs持续存在，以始终维持EPCs。我们表明，Tbx3-BCs是血管依赖的IFESCs，并确定机械拉伸是血管驱动EPC形成的外部信号。我们的结果揭示了血管介导的IFESC调控机制，这解释了表皮如何与动态皮肤中的真皮成分协调调整其大小。
