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

ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE247665 | GEO | 2025/07/02

REPOSITORIES: GEO

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MYCN-transformed neuroblasts from TH-MYCN mice are selectively isolated and maintained as spheres in vitro

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Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. Given the fact that neuroblastoma is derived from sympathoadrenal progenitors which are originated from neural crest stem cells, we attempted to use the well-established culture condition that has been utilized to maintain derivatives of neural crest stem cells. However, the medium contained retinoic acid (RA) which is known to induce neuroblastoma differentiation and is used in clinical treatment against high-risk patients. In the present study, the medium with RA (RA (+) medium) and without RA (RA (-) medium) were compared. Since undifferentiated neuroblasts are observable at one of the sympathetic ganglia, superior mesenteric ganglion (SMG), in 3-week-old TH-MYCN hemizygote (TH-MYCN+/-) mice with 129+Ter/SvJcl mice background, we dissected and dissociated the SMG to prepare single cells. These cells were cultured in either RA (+) or RA (-) media. Spheres formed in either RA (+) or RA (-) medium were subjected to microarray analysis.

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

Project description:Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development

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Project description:MYCN-transformed neuroblasts from TH-MYCN mice are selectively isolated and maintained as spheres in vitro

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