Prominin‐1 controls stem cell activation by orchestrating ciliary dynamics

• Donald Singer ^[9] ; Kristina Thamm ^[1] ; Heng Zhuang ^[10] ; Jana Karbanová ^[1] ; Yan Gao ^[11] ; Jemma Victoria Walker ^[9] ; Heng Jin ^[12] ; Xiangnan Wu ^[13] ; Clarissa R Coveney ^[14] ; Pauline Marangoni ^[13] ; Dongmei Lu ^[2] ; Portia Rebecca Clare Grayson ^[9] ; Tulay Gulsen ^[3] ; Karen J Liu ^[4] ; Stefano Ardu ^[5] ; Angus KT Wann ^[14] ; Shouqing Luo ^[15] ; Alexander C Zambon ^[16] ; Anton M Jetten ^[17] ; Christopher Tredwin ^[9] ; Ophir D Klein ^[18] ; Massimo Attanasio ^[6] ; Peter Carmeliet ^[7] ; Wieland B Huttner ^[8] ; Denis Corbeil ^[1] ; Bing Hu ^[9]
  1. [1] Dresden University of Technology

     Dresden University of Technology

     Kreisfreie Stadt Dresden, Alemania

     
  2. [2] University of Texas Southwestern Medical Center

     University of Texas Southwestern Medical Center

     Estados Unidos

     
  3. [3] University College London

     University College London

     Reino Unido

     
  4. [4] King's College London

     King's College London

     Reino Unido

     
  5. [5] Université de Genève

     Université de Genève

     Genève, Suiza

     
  6. [6] University of Iowa

     University of Iowa

     City of Iowa City, Estados Unidos

     
  7. [7] KU Leuven

     KU Leuven

     Arrondissement Leuven, Bélgica

     
  8. [8] Max Planck Institute of Molecular Cell Biology and Genetics

     Max Planck Institute of Molecular Cell Biology and Genetics

     Kreisfreie Stadt Dresden, Alemania

     
  9. [9] 1 Peninsula Dental School University of Plymouth Plymouth UK
  10. [10] 1 Peninsula Dental School University of Plymouth Plymouth UK; 3 Department of Cariology, Endodontology and Operative Dentistry Peking University School and Hospital of Stomatology Beijing China
  11. [11] 1 Peninsula Dental School University of Plymouth Plymouth UK; 4 Department of Orthodontics School of Stomatology Capital Medical University Beijing China
  12. [12] 5 Department of Internal Medicine University of Iowa Iowa City IA USA; 6 Department of Emergency Medicine Tianjin Medical University General Hospital Tianjin China
  13. [13] 7 Program in Craniofacial Biology and Department of Orofacial Sciences University of California San Francisco CA USA
  14. [14] 8 Arthritis Research UK Centre for Osteoarthritis Pathogenesis Kennedy Institute Nuffield Department for Orthopaedics, Rheumatology, and Musculoskeletal Sciences University of Oxford Oxford UK
  15. [15] 12 Peninsula Medical School University of Plymouth Plymouth UK
  16. [16] 13 Biopharmaceutical Sciences Keck Graduate Institute Claremont CA USA
  17. [17] 14 Cell Biology Section Division of Intramural Research National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park NC USA
  18. [18] 7 Program in Craniofacial Biology and Department of Orofacial Sciences University of California San Francisco CA USA; 15 Department of Pediatrics and Institute for Human Genetics University of California San Francisco CA USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 2, 2019, pág. 5
• Idioma: inglés
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• Resumen

  • Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly–disassembly dynamics are under rigid cell cycle‐dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol‐binding membrane glycoprotein, Prominin‐1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.