thank you!

thank you!

8/ Several important limitations: 1) the human cells are immature at these stages (~mid-fetal); 2) we did not observe clear cortical lamination or arealization; 3) many cell populations found in mature cortex are absent or underrepresented (e.g. interneuron subtypes)

7/ The ability to measure behavioral outputs in XCX motivated us to model outcomes in a hypoxia paradigm. Hypoxic injury to the engrafted cells produced measurable behavioral phenotypes in the host, providing a behavioral readout of damage to human neurons.

6/ Unbiased (MoSeq) and targeted behavioral measurements revealed broadly preserved locomotion and subtle differences in limb coordination and spontaneous behavior. Consistent with other studies, apallial mice have remarkably preserved behavioral phenotypes.

5/ Through wonderful collaborations (Tilo Gschwind in Ivan Soltesz lab; @deisseroth.bsky.social) we were able to measure spontaneous, highly correlated, XCX neural activity in vivo through graft-wide calcium activity reminiscent of developing circuits.

4/ One surprising finding in XCX tissue, which we hadn’t seen before, was the generation of L5-ET neurons, which contain corticospinal neurons. We also found features of Von Economo-like neurons (a population that is enriched in large brain mammals).

3/ We transplanted human cortical organoids into the cortical cavity of these apallial mice (in the immunodeficient SCID background) and remarkably the human tissue grew to cover most of mouse cortical volume. We call these animals xenocortical mice (XCX).