堀口 健太郎

Craniopharyngiomas, including adamantinomatous (ACP) and squamous papillary (PCP) types, are challenging to treat because of their proximity to crucial pituitary structures. This study aimed to characterize the cellular composition, tumor tissue diversity, and cell-cell interactions in ACPs and PCPs using single-cell RNA sequencing. Single-cell clustering revealed diverse cell types, further classified into developing epithelial, calcification, and immune response for ACP and developing epithelial, cell cycle, and immune response for PCP, based on gene expression patterns. Subclustering revealed the enrichment of classical M1 and M2 macrophages in ACP and PCP, respectively, with high expression of pro-inflammatory markers in classical M1 macrophages. The classical M1 and M2 macrophage ratio significantly correlated with the occurrence of diabetes insipidus and panhypopituitarism. Cell-cell interactions, particularly involving CD44-SPP, were identified between tumor cells. Thus, we developed a comprehensive cell atlas that elucidated the molecular characteristics and immune cell inter-networking in ACP and PCP tumor microenvironments.

エナメル上皮型頭蓋咽頭腫の病態については、これまでCTNNB1変異に伴うWnt signal活性など少しずつ解明が進んでいるが、まだ全容解明には至っていない。その要因の一つとして、腫瘍内部は非常にheterogeneityに富んでおり、これまでのbulk検体を対象とした検討では腫瘍細胞本来の性質が隠されてしまうことが挙げられる。今回、この問題をブレイクスルーするシングルセル解析法を用いて本症の病態解明を試みた。その結果、本症の腫瘍細胞には2つのsubtype(Immune rich typeとProliferative epithelial type)があり、それぞれ異なる分子生物学的背景が存在することが明らかになった。