Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.

Yuan, X; Seneviratne, JA; Du, S; Xu, Y; Chen, Y; Jin, Q; Jin, X; Balachandran, A; Huang, S; Xu, Y; Zhai, Y; Lu, L; Tang, M; Dong, Y; Cheung, BB; Marshall, GM; Shi, W; Carter, DR; Zhang, C

Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.

Yuan, X Seneviratne, JA Du, S Xu, Y Chen, Y Jin, Q Jin, X Balachandran, A Huang, S Xu, Y Zhai, Y Lu, L Tang, M Dong, Y Cheung, BB Marshall, GM Shi, W Carter, DR Zhang, C

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Cell Rep, 2022, 41, (1), pp. 111455
Issue Date:: 2022-10-04

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Field	Value	Language
dc.contributor.author	Yuan, X
dc.contributor.author	Seneviratne, JA
dc.contributor.author	Du, S
dc.contributor.author	Xu, Y
dc.contributor.author	Chen, Y
dc.contributor.author	Jin, Q
dc.contributor.author	Jin, X
dc.contributor.author	Balachandran, A
dc.contributor.author	Huang, S
dc.contributor.author	Xu, Y
dc.contributor.author	Zhai, Y
dc.contributor.author	Lu, L
dc.contributor.author	Tang, M
dc.contributor.author	Dong, Y
dc.contributor.author	Cheung, BB
dc.contributor.author	Marshall, GM
dc.contributor.author	Shi, W
dc.contributor.author	Carter, DR
dc.contributor.author	Zhang, C
dc.date.accessioned	2023-04-12T01:43:56Z
dc.date.available	2022-09-14
dc.date.available	2023-04-12T01:43:56Z
dc.date.issued	2022-10-04
dc.identifier.citation	Cell Rep, 2022, 41, (1), pp. 111455
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/169619
dc.description.abstract	Peripheral neuroblastic tumors (PNTs) represent a spectrum of neural-crest-derived tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Malignant cells in PNTs are theorized to interconvert between adrenergic/noradrenergic and mesenchymal/neural crest cell states. Here, single-cell RNA-sequencing analysis of 10 PNTs demonstrates extensive transcriptomic heterogeneity. Trajectory modeling suggests that malignant neuroblasts move between adrenergic and mesenchymal cell states via an intermediate state that we term "transitional." Transitional cells express programs linked to a sympathoadrenal development and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature is predictive of poor prognosis compared with adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identifies a similar transitional H3K27-acetylation super-enhancer landscape. Collectively, our study supports the concept that PNTs have phenotypic plasticity and uncovers potential biomarkers and therapeutic targets.
dc.format	Print
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Cell Rep
dc.relation.isbasedon	10.1016/j.celrep.2022.111455
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.subject.mesh	Adrenergic Agents
dc.subject.mesh	Ganglioneuroblastoma
dc.subject.mesh	Ganglioneuroma
dc.subject.mesh	Humans
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	RNA
dc.subject.mesh	Humans
dc.subject.mesh	Ganglioneuroma
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	Ganglioneuroblastoma
dc.subject.mesh	RNA
dc.subject.mesh	Adrenergic Agents
dc.subject.mesh	Adrenergic Agents
dc.subject.mesh	Ganglioneuroblastoma
dc.subject.mesh	Ganglioneuroma
dc.subject.mesh	Humans
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	RNA
dc.title	Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.
dc.type	Journal Article
utslib.citation.volume	41
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
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/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-04-12T01:43:52Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	41
utslib.citation.issue	1

Abstract:

Peripheral neuroblastic tumors (PNTs) represent a spectrum of neural-crest-derived tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Malignant cells in PNTs are theorized to interconvert between adrenergic/noradrenergic and mesenchymal/neural crest cell states. Here, single-cell RNA-sequencing analysis of 10 PNTs demonstrates extensive transcriptomic heterogeneity. Trajectory modeling suggests that malignant neuroblasts move between adrenergic and mesenchymal cell states via an intermediate state that we term "transitional." Transitional cells express programs linked to a sympathoadrenal development and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature is predictive of poor prognosis compared with adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identifies a similar transitional H3K27-acetylation super-enhancer landscape. Collectively, our study supports the concept that PNTs have phenotypic plasticity and uncovers potential biomarkers and therapeutic targets.

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http://hdl.handle.net/10453/169619