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Signal requirement for cortical potential of transplantable human neuroepithelial stem cells.
Varga, Balazs V; Faiz, Maryam; Pivonkova, Helena; Khelifi, Gabriel; Yang, Huijuan; Gao, Shangbang; Linderoth, Emma; Zhen, Mei; Karadottir, Ragnhildur Thora; Hussein, Samer M; Nagy, Andras.
Afiliación
  • Varga BV; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. bv243@cam.ac.uk.
  • Faiz M; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge, UK. bv243@cam.ac.uk.
  • Pivonkova H; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Khelifi G; Department of Surgery, Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
  • Yang H; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge, UK.
  • Gao S; Cancer Research Center, Université Laval, Quebec City, QC, Canada.
  • Linderoth E; CHU of Québec-Université Laval Research Center, Oncology Division, Quebec City, QC, Canada.
  • Zhen M; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Karadottir RT; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Hussein SM; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Nagy A; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Nat Commun ; 13(1): 2844, 2022 05 23.
Article en En | MEDLINE | ID: mdl-35606347
The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-ß1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucógeno Sintasa Quinasa 3 / Células Neuroepiteliales Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucógeno Sintasa Quinasa 3 / Células Neuroepiteliales Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido