@article{dd21f6b604d54ae1b62fbf7d6ddbd283,
title = "Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs",
abstract = "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.",
author = "R. Ichijo and M. Kabata and H. Kidoya and F. Muramatsu and R. Ishibashi and K. Abe and K. Tsutsui and H. Kubo and Y. Iizuka and S. Kitano and H. Miyachi and Y. Kubota and H. Fujiwara and A. Sada and T. Yamamoto and F. Toyoshima",
note = "Funding Information: Mice were maintained on a C57BL/6 genetic background. Eight-to 12-week-old male mice were used for plantar skin experiments and skin stretch assays. All other experiments were performed using 8-to 12-week-old female mice. The Tbx3creERT2 strain was generated as described below. RosatdTomato (39), K5-tTA (40), pTRE-H2B-GFP (17), K14creERT2 (25), K14–VEGF-A (30), and VEGFR2flox/flox (41) strains were obtained from the Jackson laboratories. The R26H2B-EGFP strain (42) (CDB0203K; www2.clst.riken.jp/arg/reporter_mice.html) was obtained from RIKEN Center for Developmental Biology. The Hbegf flox/flox (43) (RBRC01308) strain was provided by RIKEN BioResource Research Center through the National Bio-Resource Project of Ministry of Education, Culture, Sports, Science and Technology, Japan. VE-cadherin-CreER strain was generated previously (44). Adam8 KO (18) and Tbx3flox/flox (45) strains were provided by J. W. Bartsch (Philipps University Marburg) and A. Moon (University of Utah), respectively. All experiments were performed in accordance with the guidelines of the Kyoto University Regulation on Animal Experimentation. The animal experiments were approved by the Committee for Animal Experiments of the Institute for Frontier Life and Medical Sciences, Kyoto University. The sample size was chosen by experimental consideration and not a statistical method. The experiments were not randomized. Investigators were not blinded to allocation during experiments and outcome assessment. Funding Information: This work was supported by JSPS KAKENHI 16H06280 (to R.Ic.), 17H06809 (to R.Ic.), 19K17796 (to R.Ic.), 17H05640 (to F.T.), 16H06279 (to F.T.), and 19H03681 (to F.T.); AMED under grant number JP20gm5810029 (to F.T.); the KAO Foundation for Arts and Sciences (to R.Ic.); the Takeda Science Foundation (to F.T.); the Cell Science Research Foundation (to F.T.); and the Joint Usage/Research Center Program of Institute for Frontier Life and Medical Sciences Kyoto University (to A.S.). Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2021",
month = feb,
day = "10",
doi = "10.1126/sciadv.abd2575",
language = "English",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "7",
}