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Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus.
Rasetto, Natalí B; Giacomini, Damiana; Berardino, Ariel A; Waichman, Tomás Vega; Beckel, Maximiliano S; Di Bella, Daniela J; Brown, Juliana; Davies-Sala, M Georgina; Gerhardinger, Chiara; Lie, Dieter Chichung; Arlotta, Paola; Chernomoretz, Ariel; Schinder, Alejandro F.
Afiliação
  • Rasetto NB; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
  • Giacomini D; Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina.
  • Berardino AA; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
  • Waichman TV; Laboratory of Neuronal Plasticity, Leloir Institute, Buenos Aires, Argentina.
  • Beckel MS; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
  • Di Bella DJ; Laboratory of Integrative Systems Biology, Leloir Institute, Buenos Aires, Argentina.
  • Brown J; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
  • Davies-Sala MG; Laboratory of Integrative Systems Biology, Leloir Institute, Buenos Aires, Argentina.
  • Gerhardinger C; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
  • Lie DC; Laboratory of Integrative Systems Biology, Leloir Institute, Buenos Aires, Argentina.
  • Arlotta P; Department of Stem Cells and Regenerative Biology, Harvard University and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chernomoretz A; Department of Stem Cells and Regenerative Biology, Harvard University and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Schinder AF; Instituto de Investigaciones Biomédicas de Buenos Aires (IIBBA) - CONICET, Buenos Aires, Argentina.
Sci Adv ; 10(29): eadp6039, 2024 Jul 19.
Article em En | MEDLINE | ID: mdl-39028813
ABSTRACT
The adult hippocampus generates new granule cells (aGCs) with functional capabilities that convey unique forms of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like cells (RGLs) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to study aGC differentiation using single-nuclei RNA sequencing. Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple immature stages bearing increasing levels of effector genes supporting growth, excitability, and synaptogenesis. Analysis of differential gene expression, pseudo-time trajectory, and transcription factors (TFs) revealed critical transitions defining four cellular states quiescent RGLs, proliferative progenitors, immature aGCs, and mature aGCs. Becoming mature aGCs involved a transcriptional switch that shuts down pathways promoting cell growth, such SoxC TFs, to activate programs that likely control neuronal homeostasis. aGCs overexpressing Sox4 or Sox11 remained immature. Our results unveil precise molecular mechanisms driving adult RGLs through the pathway of neuronal differentiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Fatores de Transcrição SOXC / Neurogênese / Hipocampo / Neurônios Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Fatores de Transcrição SOXC / Neurogênese / Hipocampo / Neurônios Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos