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1.
Nat Neurosci ; 27(2): 359-372, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38263460

RESUMEN

The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations are unknown. To fill this gap, we profiled the single-cell transcriptome of adult Drosophila brains across the sleep-wake cycle and four circadian times. We show cell type-specific transcriptomic changes, with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep-wake cycle and sleep drive level affect the expression of clock gene regulators in glia, and disrupting clock genes specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings provide a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep-wake dynamics.


Asunto(s)
Ritmo Circadiano , Sueño , Animales , Ritmo Circadiano/genética , Sueño/genética , Privación de Sueño/genética , Perfilación de la Expresión Génica , Neuroglía , Vigilia
2.
Science ; 362(6416)2018 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-30309905

RESUMEN

Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Lastly, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modeling of cortical development, physiology, and pathogenesis.


Asunto(s)
Corteza Cerebral/embriología , Síndrome de Down/embriología , Modelos Biológicos , Neurogénesis , Plasticidad Neuronal , Neuronas/fisiología , Animales , Axones/fisiología , Axones/ultraestructura , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/ultraestructura , Síndrome de Down/patología , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/fisiología , Células Madre Pluripotentes Inducidas/trasplante , Ratones , Ratones SCID , Microscopía de Fluorescencia por Excitación Multifotónica , Células-Madre Neurales/citología , Células-Madre Neurales/fisiología , Neuroglía/citología , Neuroimagen , Neuronas/patología , Neuronas/ultraestructura , Análisis de la Célula Individual , Sinapsis/fisiología
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