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Generation of Functional Human 3D Cortico-Motor Assembloids.
Andersen, Jimena; Revah, Omer; Miura, Yuki; Thom, Nicholas; Amin, Neal D; Kelley, Kevin W; Singh, Mandeep; Chen, Xiaoyu; Thete, Mayuri Vijay; Walczak, Elisabeth M; Vogel, Hannes; Fan, H Christina; Pasca, Sergiu P.
Afiliação
  • Andersen J; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Revah O; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Miura Y; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Thom N; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Amin ND; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Kelley KW; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Singh M; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Chen X; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Thete MV; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Walczak EM; BD Biosciences, 4040 Campbell Ave Suite 110, Menlo Park, CA 94025, USA.
  • Vogel H; Departments of Pathology and Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Fan HC; BD Biosciences, 4040 Campbell Ave Suite 110, Menlo Park, CA 94025, USA.
  • Pasca SP; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: spasca@stanford.edu.
Cell ; 183(7): 1913-1929.e26, 2020 12 23.
Article em En | MEDLINE | ID: mdl-33333020
ABSTRACT
Neurons in the cerebral cortex connect through descending pathways to hindbrain and spinal cord to activate muscle and generate movement. Although components of this pathway have been previously generated and studied in vitro, the assembly of this multi-synaptic circuit has not yet been achieved with human cells. Here, we derive organoids resembling the cerebral cortex or the hindbrain/spinal cord and assemble them with human skeletal muscle spheroids to generate 3D cortico-motor assembloids. Using rabies tracing, calcium imaging, and patch-clamp recordings, we show that corticofugal neurons project and connect with spinal spheroids, while spinal-derived motor neurons connect with muscle. Glutamate uncaging or optogenetic stimulation of cortical spheroids triggers robust contraction of 3D muscle, and assembloids are morphologically and functionally intact for up to 10 weeks post-fusion. Together, this system highlights the remarkable self-assembly capacity of 3D cultures to form functional circuits that could be used to understand development and disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Córtex Cerebral / Córtex Motor Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Córtex Cerebral / Córtex Motor Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article