PDF(Pubmed)
Abstract：
BACKGROUND: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed.
METHODS: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining.
RESULTS: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells.
CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.
METHODS: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining.
RESULTS: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells.
CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.
摘要：
背景：细胞衰老可以对身体产生积极和消极的影响，包括帮助损伤修复和促进肿瘤生长。Adamantinomatal颅咽管瘤（ACP），最常见的小儿鞍区/鞍上脑肿瘤，带来了重大的治疗挑战。最近的研究表明，ACP肿瘤中的衰老细胞可能通过释放与衰老相关的分泌表型（SASP）来促进肿瘤的生长和侵袭。然而,对这些特征的详细分析尚未完成。
方法：我们使用单细胞，单核,和空间RNA测序。我们进行了各种分析，包括基因表达聚类，从基因表达推断衰老细胞，并进行细胞因子信号传导推断。我们利用LASSO选择与衰老相关的必需基因表达途径。最后,我们通过免疫染色验证了我们的发现.
结果：我们观察到基因表达和组织结构的显着多样性。关键因素如NFKB，RELA,和SP1在调节基因表达方面是必不可少的，而衰老标志物存在于整个组织中。SPP1是ACP细胞中最重要的细胞因子信号网络，而Wnt信号通路主要发生在上皮细胞和神经胶质细胞之间。我们的研究已经确定了衰老相关特征和途径之间的联系，例如PI3K/Akt/mTOR，MYC,FZD,还有刺猬,这些细胞中与衰老相关的P53表达增加。
结论：细胞衰老之间的复杂相互作用，细胞因子信号，基因表达途径是ACP发育的基础。进一步的研究对于了解这些元素如何相互作用以创建针对ACP患者的新治疗方法至关重要。
方法：我们使用单细胞，单核,和空间RNA测序。我们进行了各种分析，包括基因表达聚类，从基因表达推断衰老细胞，并进行细胞因子信号传导推断。我们利用LASSO选择与衰老相关的必需基因表达途径。最后,我们通过免疫染色验证了我们的发现.
结果：我们观察到基因表达和组织结构的显着多样性。关键因素如NFKB，RELA,和SP1在调节基因表达方面是必不可少的，而衰老标志物存在于整个组织中。SPP1是ACP细胞中最重要的细胞因子信号网络，而Wnt信号通路主要发生在上皮细胞和神经胶质细胞之间。我们的研究已经确定了衰老相关特征和途径之间的联系，例如PI3K/Akt/mTOR，MYC,FZD,还有刺猬,这些细胞中与衰老相关的P53表达增加。
结论：细胞衰老之间的复杂相互作用，细胞因子信号，基因表达途径是ACP发育的基础。进一步的研究对于了解这些元素如何相互作用以创建针对ACP患者的新治疗方法至关重要。
