Maturation and circuit integration of transplanted human cortical organoids

Revah, Omer; Gore, Felicity; Kelley, Kevin W.; Andersen, Jimena; Sakai, Noriaki; Chen, Xiaoyu; Li, Min-Yin; Birey, Fikri; Yang, Xiao; Saw, Nay L.; Baker, Samuel W.; Amin, Neal D.; Kulkarni, Shravanti; Mudipalli, Rachana; Cui, Bianxiao; Nishino, Seiji; Grant, Gerald A.; Knowles, Juliet K.; Shamloo, Mehrdad; Huguenard, John R.; Deisseroth, Karl; Pașca, Sergiu P.

doi:10.1038/s41586-022-05277-w

articleNatureOct 12, 2022HYBRID OA

Maturation and circuit integration of transplanted human cortical organoids

OROmer Revah FGFelicity Gore KWKevin W. Kelley JAJimena Andersen NSNoriaki Sakai

Neurosciences Institute · Organogenesis (United States) · +3 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane…

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Topics

Keywords

Organoid
Neuroscience
Optogenetics
Somatosensory system
Biology
Transplantation
Neural stem cell
Biological neural network

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