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Xenograft-specific transcriptional profiling for the characterisation of human pluripotent stem cell-derived neural transplants in the rodent brain

ABSTRACT: Here we aim to demonstrate a novel approach enabling standardised and rapid characterisation of transplanted xenografts in the rodent brain. The approach employs bulk tissue dissection, inclusive of the grafted human cells and surrounding host (rodent) tissue, and utilises differences in the RNA sequences between the species to discriminate the xenograft from host gene expression. To demonstrate and validate this technique, we assessed grafts of undifferentiated human stem cells, immature neural progenitors and mature neurons following transplantation into the rodent brain. Mixed species RNAseq was conducted on the bulk dissected tissue, and a high stringency analysis pipeline developed to discriminate the human reads. Xenograft-specific RNAseq allowed accurate profiling the complete transcriptome of the transplant with high sensitivity and accuracy. The profile allowed the identification of novel gene expression and an unbiased characterisation of graft composition, providing a valuable tool for the analysis of xenografts. This characterisation will be especially crucial for the characterisation of grafts in pre-clinical and batch testing of therapeutic cell preparations prior to translation to the clinic.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE126804 | GEO | 2019/08/31

REPOSITORIES: GEO

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