Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.

Tsubota, S; Carter, DR; Seneviratne, JA; Hirose, H; Shimamura, T; Kashima, Y; Suzuki, Y; Tsuda, K; Marshall, GM; Kadomatsu, K

Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.

Tsubota, S Carter, DR Seneviratne, JA Hirose, H Shimamura, T Kashima, Y Suzuki, Y Tsuda, K Marshall, GM Kadomatsu, K

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Publisher:: Oxford University Press (OUP)
Publication Type:: Journal Article
Citation:: Neuro Oncol, 2025, 27, (10), pp. 2671-2683
Issue Date:: 2025-10-01

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Field	Value	Language
dc.contributor.author	Tsubota, S
dc.contributor.author	Carter, DR
dc.contributor.author	Seneviratne, JA
dc.contributor.author	Hirose, H
dc.contributor.author	Shimamura, T
dc.contributor.author	Kashima, Y
dc.contributor.author	Suzuki, Y
dc.contributor.author	Tsuda, K
dc.contributor.author	Marshall, GM
dc.contributor.author	Kadomatsu, K
dc.date.accessioned	2026-04-29T04:51:34Z
dc.date.available	2026-04-29T04:51:34Z
dc.date.issued	2025-10-01
dc.identifier.citation	Neuro Oncol, 2025, 27, (10), pp. 2671-2683
dc.identifier.issn	1522-8517
dc.identifier.issn	1523-5866
dc.identifier.uri	http://hdl.handle.net/10453/194827
dc.description.abstract	BACKGROUND: Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer. METHODS: Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma. Single-cell transcriptomic analysis of ganglion tissues from Th-MYCN mice was conducted to elucidate the cellular and molecular underpinnings. RESULTS: Trajectory analysis of pre-cancerous neuroblasts revealed a distinct subtype we designated as "uncommitted" cells, characterized by the expression of neuronal genes, indicative of a semi-differentiated state. Samples with predicted failed tumorigenesis had a greater proportion of these uncommitted cells, hinting at their association with spontaneous regression. In clinical specimens, heightened uncommitted gene expression corresponded with favorable neuroblastomas and an improved prognosis. CONCLUSION: Collectively, the identification of this novel neuroblastoma-related cell subtype and its transcriptomic signature not only enhances our understanding of spontaneous regression mechanisms but also holds potential for therapeutic advancements in treating neuroblastomas.
dc.format	Print
dc.language	eng
dc.publisher	Oxford University Press (OUP)
dc.relation.ispartof	Neuro Oncol
dc.relation.isbasedon	10.1093/neuonc/noaf129
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1109 Neurosciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.subject.classification	3211 Oncology and carcinogenesis
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	Animals
dc.subject.mesh	N-Myc Proto-Oncogene Protein
dc.subject.mesh	Mice
dc.subject.mesh	Humans
dc.subject.mesh	Prognosis
dc.subject.mesh	Transcriptome
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Prognosis
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Transcriptome
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	N-Myc Proto-Oncogene Protein
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	Animals
dc.subject.mesh	N-Myc Proto-Oncogene Protein
dc.subject.mesh	Mice
dc.subject.mesh	Humans
dc.subject.mesh	Prognosis
dc.subject.mesh	Transcriptome
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Biomarkers, Tumor
dc.title	Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.
dc.type	Journal Article
utslib.citation.volume	27
utslib.location.activity	England
utslib.for	1109 Neurosciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-04-29T04:51:32Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	27
utslib.citation.issue	10

Abstract:

BACKGROUND: Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer. METHODS: Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma. Single-cell transcriptomic analysis of ganglion tissues from Th-MYCN mice was conducted to elucidate the cellular and molecular underpinnings. RESULTS: Trajectory analysis of pre-cancerous neuroblasts revealed a distinct subtype we designated as "uncommitted" cells, characterized by the expression of neuronal genes, indicative of a semi-differentiated state. Samples with predicted failed tumorigenesis had a greater proportion of these uncommitted cells, hinting at their association with spontaneous regression. In clinical specimens, heightened uncommitted gene expression corresponded with favorable neuroblastomas and an improved prognosis. CONCLUSION: Collectively, the identification of this novel neuroblastoma-related cell subtype and its transcriptomic signature not only enhances our understanding of spontaneous regression mechanisms but also holds potential for therapeutic advancements in treating neuroblastomas.

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http://hdl.handle.net/10453/194827