Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma.

ABSTRACT: Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly defined. We now document spontaneous and reversible plasticity between the two identities, associated with epigenetic reprogramming, in several neuroblastoma models. Interestingly, xenografts with cells from each identity eventually harbor a noradrenergic phenotype suggesting that the microenvironment provides a powerful pressure towards this phenotype. Accordingly, such a noradrenergic cell identity is systematically observed in single-cell RNA-seq of 18 tumor biopsies and 15 PDX models. Yet, a subpopulation of these noradrenergic tumor cel

SUBMITTER: Thirant C 

PROVIDER: S-EPMC10160107 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature