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Unraveling epithelial cell heterogeneity in adamantinomatous craniopharyngioma using single-cell and spatially resolved analysis

ABSTRACT: Unraveling epithelial cell heterogeneity in adamantinomatous craniopharyngioma using single-cell and spatially resolved analysis

PROVIDER: PRJNA891311 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21935008.fastq.gz	Fastqsanger.gz
	SRR21935009.fastq.gz	Fastqsanger.gz
	SRR21935010.fastq.gz	Fastqsanger.gz
	SRR21935011.fastq.gz	Fastqsanger.gz
	SRR21935012.fastq.gz	Fastqsanger.gz

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Unraveling epithelial cell heterogeneity in adamantinomatous craniopharyngioma using single-cell and spatially resolved analysis

Project description:Adamantinomatous craniopharyngioma (ACP) is an intractable and histologically complex epithelial neoplasm with variable pathognomonic features, while its cellular composition, particularly the epithelial component, is poorly characterized. Herein, a single-nucleus transcriptome atlas specific to ACP was constructed by performing a single-nucleus RNA sequencing (snRNA-seq) survey of 55967 nuclei in 6 ACP samples from 3 patients. We revealed 6 epithelial subtypes with diverse molecular functions in ACP by integrating snRNA-seq, spatial transcriptomic (ST) and immunostaining data. Additionally, we investigated the potential regulatory mechanism of ACP calcification by performing a trajectory analysis and transcription factor regulon analysis. Finally, we characterized the molecular characteristics of neurons and discovered potential epithelial cell–neuron crosstalk in ACP tissues. Overall, this large-scale single-nucleus atlas combined with ST provides, for the first time, unprecedented insights into epithelial cell heterogeneity within ACP and can serve as a resource for further investigation of tumor dynamics.

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Laser Capture Microdissection and RNA Sequencing Human Adamantinomatous Craniopharyngioma

Project description:Laser capture microdissection of cluster cells, palisading epithelium and glial tissue from 2 cases of human adamantinomatous craniopharyngioma. 1 case performed in duplicate.

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RNA Sequencing of Adamantinomatous Craniopharyngioma

Project description:RNA Sequencing of Adamantinomatous Craniopharyngioma

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Tumor DNA methylation profiling of patients with Adamantinomatous craniopharyngioma (ACP)

Project description:Abnormal DNA methylation plays a role in tumor progression and is becoming recognized as a prognostic marker in various types of cancers. In this study, we aimed to investigate the association between DNA methylation and clinicopathological features, prognosis, and outcomes in patients with Adamantinomatous craniopharyngioma (ACPs). To achieve this, we analyzed the global methylation profile of 35 tumors using the Illumina Infinium HumanMethylation850 BeadChip.

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Laser Capture Microdissection and RNA Sequencing Human Adamantinomatous Craniopharyngioma

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Molecular analyses reveal an inflammatory response in the solid component and cystic fluid of human adamantinomatous craniopharyngioma

Project description:Pediatric adamantinomatous craniopharyngioma (ACP) cyst may be associated with injury to critical neurological structures, such as the hypothalamus, resulting in poor quality of life and shorter lifespan. This work presents evidence that immune actors, both pro-inflammatory and immunomodulatory, and their receptors, are present at unique levels in ACP cyst fluid and tumor tissue, potentially indicating a mechanism underlying cyst growth and tumor invasion of the hypothalamus. Transcriptomic analysis revealed that ACP, when compared to other pediatric brain tumors and nomral brain, harbored overexpression of a number of inflammatory and immunosuppressive genes.

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Tumor DNA methylation profiling of patients with Adamantinomatous craniopharyngioma (ACP)

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Disruption of the Wnt-antagonist APC in the pituitary stem cells drives adamantinomatous craniopharyngioma

Project description:Disruption of the Wnt-antagonist APC in the pituitary stem cells drives adamantinomatous craniopharyngioma

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Disruption of the Wnt-antagonist APC in the pituitary stem cells drives adamantinomatous craniopharyngioma

Project description:Adamantinomatous craniopharyngioma (aPCs) are complex intracranial neoplasms that arise in the sellar or parasellar region affecting the endocrine system and leading to severe comorbidities. Activating mutations resulting in degradation resistant from of b-Catenin (CTNNB1 gene) have been shown to be the main driver for a large proportion of these neoplasms. However, the underlying genetic driver for a proportion of these tumours is still unknown. Using murine transgenic models, we show that genetic deletion of the Wnt-antagonist and tumour suppressor, Adenomatous Polyposis Coli (Apc) within the pituitary progenitors/stem cells leads to pituitary tumours that closely resemble human aCPs. These tumours present classical histopathological hallmarks of aCPs such as clusters of accumulating nuclear b-catenin that are slow dividing and undergo secretory phenotype. These tumours present wet keratin, stellar-reticular-like structures and cystic components. We show that a hypomorphic allele of Apc is sufficient for tumour development indicating that disruption of Apc function can lead to aCP formation independent of b-Catenin mutations. Moreover, we identify that bi-allelic loss of Apc in the Sox2+ve pituitary stem cells is sufficient to initiate tumour formation, indicating that Sox2+ve stem cells are the cell origin of these Apc-driven tumours. Transcriptomic analyses of early tumour-initiating cells reveal that clusters of accumulating b-Catenin, undergo p21-mediated cellular senescence and that the secretory phenotype is composed of inflammasome, angiosome and developmental growth factors which are different from the b-Catenin-driven aCP tumours. Our data, unequivocally shows, that disruption of the tumour suppressor Apc in the pituitary progenitors/stem cells is a main driver of aCPs independent of mutations in b-Catenin. We provide two novel murine models that represents a genetic subtype of aCPs which helps to further understand aCP pathogenesis.

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