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Omer Revah, Felicity Gore, Kevin W. Kelley, Jimena Andersen, Noriaki Sakai, Xiaoyu Chen, Min-Yin Li, Fikri Birey, Xiao Yang, Nay Lui Saw and 12 more
. 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 properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.
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Revah, O., Gore, F., Kelley, K. W., Andersen, J., Sakai, N., Chen, X., Li, M.-Y., Birey, F., Yang, X., Saw, N. L., Baker, S. W., Amin, N. D., Kulkarni, S., Mudipalli, R., Cui, B., Nishino, S., Grant, G. A., Knowles, J. K., Shamloo, M., … Pașca, S. P. (2022). Maturation and circuit integration of transplanted human cortical organoids. Nature, 610(7931), 319–326. https://doi.org/10.1038/s41586-022-05277-w
Revah, Omer, et al. "Maturation and circuit integration of transplanted human cortical organoids." Nature, vol. 610, no. 7931, 2022, pp. 319–326, https://doi.org/10.1038/s41586-022-05277-w.
Revah, Omer, Felicity Gore, Kevin W. Kelley, Jimena Andersen, Noriaki Sakai, Xiaoyu Chen, Min-Yin Li, et al. "Maturation and circuit integration of transplanted human cortical organoids." Nature 610, no. 7931 (2022): 319–326. https://doi.org/10.1038/s41586-022-05277-w.
Revah O., Gore F., Kelley K. W. [и др.] Maturation and circuit integration of transplanted human cortical organoids // Nature. — 2022. — Vol. 610, № 7931. — P. 319–326. — URL: https://doi.org/10.1038/s41586-022-05277-w
@article{revah2022maturation,
title = {{Maturation and circuit integration of transplanted human cortical organoids}},
author = {Omer Revah and Felicity Gore and Kevin W. Kelley and Jimena Andersen and Noriaki Sakai and Xiaoyu Chen and Min-Yin Li and Fikri Birey and Xiao Yang and Nay Lui Saw and Samuel W. Baker and Neal D. Amin and Shravanti Kulkarni and Rachana Mudipalli and Bianxiao Cui and Seiji Nishino and Gerald Arthur Grant and Juliet K. Knowles and Mehrdad Shamloo and John R. Huguenard and Karl A. Deisseroth and Sergiu P. Pașca},
journal = {Nature},
year = {2022},
volume = {610},
number = {7931},
pages = {319--326},
doi = {10.1038/s41586-022-05277-w},
url = {https://doi.org/10.1038/s41586-022-05277-w}
}TY - JOUR AU - Revah, Omer AU - Gore, Felicity AU - Kelley, Kevin W. AU - Andersen, Jimena AU - Sakai, Noriaki AU - Chen, Xiaoyu AU - Li, Min-Yin AU - Birey, Fikri AU - Yang, Xiao AU - Saw, Nay Lui AU - Baker, Samuel W. AU - Amin, Neal D. AU - Kulkarni, Shravanti AU - Mudipalli, Rachana AU - Cui, Bianxiao AU - Nishino, Seiji AU - Grant, Gerald Arthur AU - Knowles, Juliet K. AU - Shamloo, Mehrdad AU - Huguenard, John R. AU - Deisseroth, Karl A. AU - Pașca, Sergiu P. TI - Maturation and circuit integration of transplanted human cortical organoids JO - Nature VL - 610 IS - 7931 SP - 319 EP - 326 PY - 2022 DA - 2022/10/12 DO - 10.1038/s41586-022-05277-w UR - https://doi.org/10.1038/s41586-022-05277-w ER -
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