@article{bibcite_46,
  author = {Konstantin Kaganovsky and Kevin Kelley and Tilo Gschwind and Paul Harary and John Kochalka and Alexander White and Garikoitz Lerma-Usabiaga and Xiaoyu Chen and Omer Revah and Felicity Gore and Ayano Aoyama and Jennifer Shadrach and Se-Jin Yoon and Alfredo Valencia and Satoe Ogawa and Noah Reis and Hannes Vogel and Brian Wandell and Julia Kaltschmidt and Ivan Soltesz and Karl Deisseroth and Sergiu Pasca},
  title = {Developmental xenocortication using human-derived organoids in mice.},
  abstract = {<p>The inaccessibility of human brain tissue\&nbsp;limits the study\&nbsp;of human development and function, a challenge that human stem-cell-derived neural models are beginning to address.\&nbsp;Transplantation of neural organoids into rodent hosts enables the in vivo\&nbsp;study of aspects of\&nbsp;human neurodevelopment and\&nbsp;circuit function, alongside behavioural phenotyping of the host animals. However, spatial limitations and competition with host circuits constrain the integration of neural organoids, which\&nbsp;is critical for studying disease. Here we establish a transplantation platform using a genetic strategy to effectively deplete glutamatergic neurons from mouse neocortex and hippocampus (apallial) and neonatally engraft the cortical cavity with human stem-cell-derived cortical organoids (hCO) to generate xenocortical mice. This leads to robust graft growth with hCOs occupying most of the cortical volume and generating a diversity of human cortical cell types, including layer 5 extratelencephalic projection neurons. Human cortical neurons integrate with the mouse nervous system, and in vivo\&nbsp;cortical graft-wide calcium imaging and electrophysiological analyses revealed patterns of organized activity resembling developing circuits. Behavioural analyses\&nbsp;of apallial and xenocortical mice revealed broadly preserved locomotion alongside selective differences in limb coordination and altered organization of spontaneous behaviour. Lastly, this\&nbsp;platform enabled behavioural readouts in a model of injury to developing human cortical cells. We envision that xenocortication will be useful for obtaining circuit- and behaviour-level readouts using human neurons to study neurodevelopment, model disease and develop therapeutics.</p>},
  year = {2026},
  journal = {Nature},
  month = {09/2026},
  issn = {1476-4687},
  doi = {10.1038/s41586-026-11032-2},
  language = {eng},
}