Dataset Information

Genomic and transcriptomic analysis of medulloblastoma

ABSTRACT: Tandem mass spectra were processed by PEAKS Studio version 8.5 to detected phosphorylation peptides of mouse cerebellum progenitor.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Neural Progenitor Cell

SUBMITTER: Zaili Luo

LAB HEAD: Q. Richard Lu

PROVIDER: PXD019067 | Pride | 2023-03-10

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 12

Publications

Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.

Luo Zaili Z Xin Dazhuan D Liao Yunfei Y Berry Kalen K Ogurek Sean S Zhang Feng F Zhang Liguo L Zhao Chuntao C Rao Rohit R Dong Xinran X Li Hao H Yu Jianzhong J Lin Yifeng Y Huang Guoying G Xu Lingli L Xin Mei M Nishinakamura Ryuichi R Yu Jiyang J Kool Marcel M Pfister Stefan M SM Roussel Martine F MF Zhou Wenhao W Weiss William A WA Andreassen Paul P Lu Q Richard QR

Nature communications 20230210 1

MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the molecular and genetic events triggering MYC amplification and malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, are the most significantly enriched recurrent alterations in MYC-driven medulloblastomas, and define high-risk subsets with poorer prognosis. Ctdnep1 ablation promotes the transformation of murine cerebellar progenitors into Myc-amp ...[more]

PMID: 36765089

Similar Datasets

Project description:Deregulated developmental processes in the cerebellum cause medulloblastoma, the most common malignant tumor of the central nervous system. About 20-30% of cases are caused by mutations increasing the activity of the Sonic hedgehog (Shh) pathway, a critical mitogen in cerebellar development. The proto-oncogene Smoothened is a key transducer of the Shh pathway. Activating mutations in Smoothened that lead to constitutive activity of the Shh pathway have been identified in human medulloblastoma. To understand the molecular and cellular effects of Smoothened variants in normal development and medulloblastoma genesis, we generated the SmoA2 transgenic mouse model which expresses the transgene exclusively in granule neuron precursors. In this study, we demonstrate how two point mutations in a single molecule can produce starkly different phenotypes as seen in comparison to our previous model, ND2:SmoA1. The SmoA2 mice have severe aberrations in cerebellar development whereas the SmoA1 mice are largely normal during development. Medulloblastomas in the SmoA2 mice develop in the dysplastic cerebellar milieu. Intriguingly, despite disruptions in the stereotypic organization of the cerebellum, the SmoA2 mice do not exhibit any overt abnormalities in motor coordination. The differences in the global transcriptional profiles downstream of SmoA1 and SmoA2 further demonstrate the distinctiveness of the two oncogenic Smoothened mutations. The SmoA2 model serves as a unique spatiotemporal tool to investigate the functional significance of the reiterative cerebellar circuitry as well as to further understand Shh pathway mechanics in cerebellar development and oncogenesis. We previously generated a SmoA1 transgenic mouse medulloblastoma model, which expresses the SmoA1 transgene driven by the GNP-specific fragment of the promoter of ND2 transcription factor leading to constitutively active Shh signaling exclusively in the cerebellum. In this study, we characterize the ND2:SmoA2 transgenic mouse model with a similarly designed transgene expressing the SmoA2 mutation. To assess transcriptional changes downstream of SmoA1 and SmoA2, we evaluated global gene expression profiles of P5 SmoA1, SmoA2 and Wt age-matched cerebella. We chose this specific developmental stage because (1) the phenotypes of SmoA1 and SmoA2 are robust and distinct at P5; (2) at P5 GNPs undergo proliferation, migration and differentiation and therefore expression profiling could capture key differences in multiple processes.

Project description:Human ingestion of microplastics (MPs) is common and inevitable due to the widespread contamination of food items, but implications on the gastric digestion of food proteins are still unknown. In this study, the interaction between pepsin and polystyrene (PS) MPs was uncovered by investigating its effect on enzyme activity and conformation while in a simulated human gastric environment. The impact on food digestion was also determined by monitoring the kinetics of protein hydrolysis through static in vitro gastric digestion of cow’s milk contaminated with PS. The binding of pepsin to PS showed that surface chemistry of MPs dictates binding affinity. The key contributor to pepsin adsorption seems to be π−π interactions between the aromatic residues and the PS phenyl rings. During quick exposure (10 minutes) of pepsin to increasing concentrations (222, 2219, 22188 particles/mL) of 10 μm PS (PS10) and 100 μm PS (PS100), total enzymatic activities were not affected remarkably. However, upon prolonged exposure at 1 and 2 hours, preferential binding of pepsin to the small, low zeta-potential PS caused structural changes in the protein which led to a significant reduction of its activity. Digestion of cow’s milk mixed with PS10 resulted in transient accumulation of larger peptides (10-35 kDa) and reduced bioavailability of short peptides (2-9 kDa) in the gastric phase. This, however, was only observed at extremely high PS10 concentration (0.3 mg/mL or 5.46E+05 particles/mL). The digestion of milk peptides, bound preferentially over pepsin on the hard corona around PS10, was delayed up to 15 minutes in comparison to bulk protein digestion. Intact caseins, otherwise rapidly digested, remained bound to PS10 in hard corona for up to 15 minutes. This work presents valuable insights regarding the interaction of MPs, food proteins, and pepsin, and their dynamics during gastric digestion which provides new knowledge and understanding on the potential risks of MPs to human health.

			Action	DRS
	YS_4_1NSC_1_PHO.mgf	Mgf
	YS_4_1NSC_1_PHO.mzXML	Mzxml
	YS_4_1NSC_1_PHO.raw	Raw
	YS_4_1NSC_2_PHO.mgf	Mgf
	YS_4_1NSC_2_PHO.mzXML	Mzxml