Human iPSC-derived cell grafts promote functional recovery by molecular interaction with stroke-injured brain

IPSC-NPC were transplanted in a mouse model of stroke. To dissect the molecular graft composition and identify graft-host interactions, single nucleus profiling of the cell transplants and host stroke tissue was performed. We identified graft differentiation preferentially towards GABAergic cells with remaining cells acquiring glutamatergic neuron, astrocyte, and NPC-like phenotypes. Interaction between graft and host transcriptome indicated that GABAergic cell grafts were primarily involved in graft-host communication through the regeneration-associated NRXN, NRG, NCAM and SLIT signalling pathways IPSC-NPC were transplanted in mice one week after stroke. Nuclei from cell grafts and stroke-injured tissue were isolated and analysed using single nucleus RNAseq