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Analysis of the early response to spinal cord injury identified a key role for mTORC1 signaling in the activation of neural stem progenitor cells.
Peñailillo, Johany; Palacios, Miriam; Mounieres, Constanza; Muñoz, Rosana; Slater, Paula G; De Domenico, Elena; Patrushev, Ilya; Gilchrist, Mike; Larraín, Juan.
Afiliación
  • Peñailillo J; Center for Aging and Regeneration, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
  • Palacios M; Center for Aging and Regeneration, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
  • Mounieres C; Center for Aging and Regeneration, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
  • Muñoz R; Center for Aging and Regeneration, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
  • Slater PG; Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • De Domenico E; Center for Aging and Regeneration, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
  • Patrushev I; The Francis Crick Institute, 1 Midland Road, London, UK.
  • Gilchrist M; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, University of Bonn, Bonn, Germany.
  • Larraín J; The Francis Crick Institute, 1 Midland Road, London, UK.
NPJ Regen Med ; 6(1): 68, 2021 Oct 22.
Article en En | MEDLINE | ID: mdl-34686684
Xenopus laevis are able to regenerate the spinal cord during larvae stages through the activation of neural stem progenitor cells (NSPCs). Here we use high-resolution expression profiling to characterize the early transcriptome changes induced after spinal cord injury, aiming to identify the signals that trigger NSPC proliferation. The analysis delineates a pathway that starts with a rapid and transitory activation of immediate early genes, followed by migration processes and immune response genes, the pervasive increase of NSPC-specific ribosome biogenesis factors, and genes involved in stem cell proliferation. Western blot and immunofluorescence analysis showed that mTORC1 is rapidly and transiently activated after SCI, and its pharmacological inhibition impairs spinal cord regeneration and proliferation of NSPC through the downregulation of genes involved in the G1/S transition of cell cycle, with a strong effect on PCNA. We propose that the mTOR signaling pathway is a key player in the activation of NPSCs during the early steps of spinal cord regeneration.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Regen Med Año: 2021 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Regen Med Año: 2021 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Estados Unidos