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Signalling by senescent melanocytes hyperactivates hair growth.
Wang, Xiaojie; Ramos, Raul; Phan, Anne Q; Yamaga, Kosuke; Flesher, Jessica L; Jiang, Shan; Oh, Ji Won; Jin, Suoqin; Jahid, Sohail; Kuan, Chen-Hsiang; Nguyen, Truman Kt; Liang, Heidi Y; Shettigar, Nitish Udupi; Hou, Renzhi; Tran, Kevin H; Nguyen, Andrew; Vu, Kimberly N; Phung, Jennie L; Ingal, Jonard P; Levitt, Katelyn M; Cao, Xiaoling; Liu, Yingzi; Deng, Zhili; Taguchi, Nobuhiko; Scarfone, Vanessa M; Wang, Guangfang; Paolilli, Kara Nicole; Wang, Xiaoyang; Guerrero-Juarez, Christian F; Davis, Ryan T; Greenberg, Elyse Noelani; Ruiz-Vega, Rolando; Vasudeva, Priya; Murad, Rabi; Widyastuti, Lily Halida Putri; Lee, Hye-Lim; McElwee, Kevin J; Gadeau, Alain-Pierre; Lawson, Devon A; Andersen, Bogi; Mortazavi, Ali; Yu, Zhengquan; Nie, Qing; Kunisada, Takahiro; Karin, Michael; Tuckermann, Jan; Esko, Jeffrey D; Ganesan, Anand K; Li, Ji; Plikus, Maksim V.
Afiliación
  • Wang X; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA. xiaojiw2@uci.edu.
  • Ramos R; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA. xiaojiw2@uci.edu.
  • Phan AQ; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, USA. xiaojiw2@uci.edu.
  • Yamaga K; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Flesher JL; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Jiang S; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, USA.
  • Oh JW; Glycobiology Research and Training Center, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Jin S; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Jahid S; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Kuan CH; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Nguyen TK; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Liang HY; Center for Complex Biological Systems, University of California, Irvine, CA, USA.
  • Shettigar NU; Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
  • Hou R; Department of Anatomy and Hair Transplantation Center, Kyungpook National University and Hospital, Daegu, Korea.
  • Tran KH; Department of Mathematics, University of California, Irvine, CA, USA.
  • Nguyen A; School of Mathematics and Statistics, Wuhan University, Wuhan, China.
  • Vu KN; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Phung JL; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Ingal JP; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Levitt KM; Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
  • Cao X; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
  • Liu Y; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Deng Z; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Taguchi N; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Scarfone VM; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Wang G; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Paolilli KN; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Wang X; Amplifica Holdings Group, Inc., San Diego, CA, USA.
  • Guerrero-Juarez CF; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Davis RT; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Greenberg EN; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, USA.
  • Ruiz-Vega R; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Vasudeva P; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Murad R; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Widyastuti LHP; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Lee HL; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • McElwee KJ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Gadeau AP; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Lawson DA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Andersen B; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Mortazavi A; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Yu Z; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Nie Q; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Kunisada T; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Karin M; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Tuckermann J; Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
  • Esko JD; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
  • Ganesan AK; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • Li J; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • Plikus MV; Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan.
Nature ; 618(7966): 808-817, 2023 Jun.
Article en En | MEDLINE | ID: mdl-37344645
ABSTRACT
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Cabello / Melanocitos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Cabello / Melanocitos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos