Fig. 5

Per-spot gene activity enrichment analysis depicts the spatial localisation of SHH MB neuronal differentiation, progenitor and cell cycle in response to Palbociclib. a Violin plots of the per-spot SHH-A (cell cycle) gene signature activity, separated by Palbociclib A, Palbociclib B, Control C and Control D samples (left to right). *** indicates p-value < 0.001 when comparing these scores between Palbociclib-treated and control samples using a pseudosampling approach with two-tailed t-test (see ‘Methods’). b SHH-A (cell cycle) gene signature enrichment scores in Palbociclib A, Palbociclib B, Control C and Control D samples in their spatial context. Spots are coloured according to enrichment scores, from bright yellow (high gene set activity) to purple (low gene set activity). c–f Each row of panels is equivalent to the first row described above (panels a, b), except the middle row (panels c, d) indicates enrichment scores for the SHH-B progenitor cell signature, while the bottom row (panels e, f) indicates enrichment scores for the SHH-C neuronal differentiated signature. Both of these latter signatures also showed significant difference (indicated by ***), with SHH-B showing significant downregulation and SHH-C showing significant upregulation in response to Palbociclib treatment. g Automated annotation of human/mix spots using pattern matching against a reference scRNA-seq dataset from 13-week-old male foetal human brain. Annotations indicate proliferative cells at the tumour human-mouse interface in treated samples with neuronal cells at the tumour core, while proliferative cells are observed throughout untreated samples. h Comparision between pathologist annotations from H&E images (left) and per-spot enrichment of DE neuron differentiation genes and SHH-C (neuronal) signature subpopulation in Palbociclib A. Yellow circles indicate the ‘pale island’ regions annotated independently by a pathologist based on histology