Single cell RNA-seq shows cellular heterogeneity and lineage expansion in a mouse model of SHH-driven medulloblastoma support resistance to SHH inhibitor therapy

Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq, we analyzed cellular diversity and lineage in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. Overall design: Drop-Seq single-cell transcriptome sequencing of 15 mice: 5 Wild Type cerebella, 5 Drug-treated cerebellar tumors and 5 vehicle-treated cerebellar tumros.

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Ocasio J, Babcock B, Malawsky D, Weir SJ, Loo L, Simon JM, Zylka MJ, Hwang D, Dismuke T, Sokolsky M, Rosen EP, Vibhakar R, Zhang J, Saulnier O, Vladoiu M, El-Hamamy I, Stein LD, Taylor MD, Smith KS, Northcott PA, Colaneri A, Wilhelmsen K, Gershon TR