Single-cell multi-omics analysis identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma [Multiome]

We perform scMultiomic sequencing on matched patient primary and recurrent tumors. We identify a unique population of cells that is metabolically and epigenetically altered. We recapitulate this population of cells in in vivo radiation resistant models. Disruption of this population with wtIDH1 inhibitors suppresses growth and re-sensitizes cells to irradiation. Overall design: We isolated nuclei from matched primary and recurrent group 3 and group 4 MB tumors according to 10xGenomics protocol for cyropreserved tissue. Nuclei were submitted for scMultiomic sequencing.

我们对配对的患者原发与复发肿瘤开展单细胞多组学测序（scMultiomic sequencing）。本研究鉴定出一群在代谢与表观遗传层面发生改变的独特细胞群，并在体内辐射抗性模型中成功重现了该细胞群。采用野生型IDH1（wtIDH1）抑制剂靶向清除该细胞群，可抑制肿瘤生长并恢复细胞对辐射的敏感性。
整体实验设计：我们依照10xGenomics针对低温保存组织的实验流程，从配对的3型与4型髓母细胞瘤（MB）患者的原发及复发肿瘤中分离细胞核，随后将分离得到的细胞核进行单细胞多组学测序（scMultiomic sequencing）。