Cell plasticity in neuroblastoma
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ABSTRACT:
PROVIDER: PRJNA647862 | ENA |
REPOSITORIES: ENA
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Project description:Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain poorly defined. Our results now document spontaneous plasticity in several neuroblastoma models between noradrenergic and mesenchymal tumor states and show that this plasticity is reversible and relies on epigenetic reprogramming. We demonstrate that an in vivo microenvironment provides a powerful pressure towards a noradrenergic identity for these models. Interestingly, single-cell RNA-seq analyses of 18 tumor biopsies and 15 PDX models revealed that tumor cells systematically exhibit a noradrenergic identity. Yet, our data highlight a population of noradrenergic tumor cells with mesenchymal features, demonstrating that the plasticity described in cellular models between both identities is relevant in neuroblastoma patients. Our work also emphasizes that both external cues of the environment and intrinsic factors influence plasticity and cell identity in neuroblastoma.
2023-03-27 | GSE154907 | GEO
Project description:High-risk neuroblastoma is a pediatric malignancy marked by poor prognosis, high metastatic potential, and resistance to conventional therapies. Phenotypic plasticity between noradrenergic and mesenchymal cell states, each defined by specific transcriptional and epigenetic programs and distinct cellular properties, is observed in some neuroblastoma cell lines. Yet the drivers of this plasticity are not fully understood. This study identifies YAP and TAZ as central regulators of the mesenchymal state. YAP/TAZ, in complex with TEAD, FOSL, and RUNX transcription factors, establish a core regulatory circuitry associated with mesenchymal-specific super-enhancers. Expression of a conserved YAP/TAZ gene signature increases during the noradrenergic-to-mesenchymal transition and decreases during the reverse in plasticity models. Genetic or pharmacological inactivation of YAP/TAZ abrogates cellular proliferation and inhibits the noradrenergic-to-mesenchymal transition. Conversely, overexpression of YAP/TAZ in noradrenergic cells induces a major transcriptional reprogramming towards a mesenchymal state, via a redistribution of TEAD4 and a rewiring of the epigenetic landscape. These findings uncover a YAP/TAZ-TEAD4 driven epigenetic mechanism underlying tumor cell plasticity in neuroblastoma.
2026-05-10 | GSE292597 | GEO
Project description:Spontaneous and reversible plasticity between two tumor cell states, noradrenergic and mesenchymal, has been described in neuroblastoma cell lines. Here, we show that YAP, TAZ, and their target genes are marked by super-enhancers and are strongly and specifically expressed in mesenchymal tumor cells. We characterize a core regulatory circuitry containing YAP/TAZ, TEAD, FOSL and RUNX factors that controls gene expression linked to a mesenchymal identity in neuroblastoma. Genetic or pharmacological inactivation of YAP/TAZ reduces cell proliferation of mesenchymal neuroblastoma cells. The expression of a YAP/TAZ gene signature fully correlates with a mesenchymal identity in several models exhibiting plasticity between noradrenergic and mesenchymal states. Whereas YAP/TAZ inhibition impairs the noradrenergic to mesenchymal transition, YAP and/or TAZ overexpression induces a mesenchymal shift traduced by transcriptional and functional reprogramming, accompanied by the repression of noradrenergic identity. Altogether, these findings uncover a neuroblastoma-specific YAP/TAZ core regulatory circuitry controlling the switch of cell state towards a mesenchymal identity in neuroblastoma.
2026-05-10 | GSE292598 | GEO
Project description:Spontaneous and reversible plasticity between two tumor cell states, noradrenergic and mesenchymal, has been described in neuroblastoma cell lines. Here, we show that YAP, TAZ, and their target genes are marked by super-enhancers and are strongly and specifically expressed in mesenchymal tumor cells. We characterize a core regulatory circuitry containing YAP/TAZ, TEAD, FOSL and RUNX factors that controls gene expression linked to a mesenchymal identity in neuroblastoma. Genetic or pharmacological inactivation of YAP/TAZ reduces cell proliferation of mesenchymal neuroblastoma cells. The expression of a YAP/TAZ gene signature fully correlates with a mesenchymal identity in several models exhibiting plasticity between noradrenergic and mesenchymal states. Whereas YAP/TAZ inhibition impairs the noradrenergic to mesenchymal transition, YAP and/or TAZ overexpression induces a mesenchymal shift traduced by transcriptional and functional reprogramming, accompanied by the repression of noradrenergic identity. Altogether, these findings uncover a neuroblastoma-specific YAP/TAZ core regulatory circuitry controlling the switch of cell state towards a mesenchymal identity in neuroblastoma.
2026-05-10 | GSE292595 | GEO
Project description:Targeting SWI/SNF ATPases reduces neuroblastoma cell plasticity
| PRJNA1004275 | ENA
Project description:Single-cell MultiOmics and spatial transcriptomics demonstrate neuroblastoma developmental plasticity
| PRJNA761770 | ENA
Project description:Malignant Schwann cell precursors mediate intratumoral plasticity in human neuroblastoma
| PRJNA616343 | ENA
Project description:Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we demonstrate that GATA3 but not PHOX2A or PHOX2B knock-out in noradrenergic cells induces a mesenchymal phenotype. We further document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines and identify transcription factors expressed in transition cells between the two states. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are not detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.
| EGAS00001005322 | EGA
Project description:Malignant Schwann cell precursors mediate intratumoral plasticity in human neuroblastoma [Array]
| PRJNA616347 | ENA
Project description:Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we demonstrate that GATA3 but not PHOX2A or PHOX2B knock-out in noradrenergic cells induces a mesenchymal phenotype. We further document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines and identify transcription factors expressed in transition cells between the two states. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are not detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.
| EGAS00001004781 | EGA