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.
journal_name
Celljournal_title
Cellauthors
Andersen J,Revah O,Miura Y,Thom N,Amin ND,Kelley KW,Singh M,Chen X,Thete MV,Walczak EM,Vogel H,Fan HC,Paşca SPdoi
10.1016/j.cell.2020.11.017subject
Has Abstractpub_date
2020-12-23 00:00:00pages
1913-1929.e26issue
7eissn
0092-8674issn
1097-4172pii
S0092-8674(20)31534-8journal_volume
183pub_type
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