Generation of Functional Human 3D Cortico-Motor Assembloids

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Dec 17

PMID 33333020

Citations 192

Authors

Jimena Andersen

Omer Revah

Yuki Miura

Nicholas Thom

Neal D Amin

Kevin W Kelley

Mandeep Singh

Xiaoyu Chen

Mayuri Vijay Thete

Elisabeth M Walczak

Hannes Vogel

H Christina Fan

Sergiu P Pasca

Affiliations

Soon will be listed here.

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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