TY - JOUR T1 - Interplay between intrinsic reprogramming potential and microenvironment controls neuroblastoma cell plasticity and identity JF - bioRxiv DO - 10.1101/2021.01.07.425710 SP - 2021.01.07.425710 AU - Cécile Thirant AU - Agathe Peltier AU - Simon Durand AU - Amira Kramdi AU - Caroline Louis-Brennetot AU - Cécile Pierre-Eugène AU - Ana Costa AU - Amandine Grelier AU - Sakina Zaïdi AU - Nadège Gruel AU - Irène Jimenez AU - Eve Lapouble AU - Gaëlle Pierron AU - Hervé J. Brisse AU - Arnaud Gauthier AU - Paul Fréneaux AU - Sandrine Grossetête-Lalami AU - Laura G. Baudrin AU - Virginie Raynal AU - Sylvain Baulande AU - Angela Bellini AU - Jaydutt Bhalshankar AU - Angel M. Carcaboso AU - Birgit Geoerger AU - Hermann Rohrer AU - Didier Surdez AU - Valentina Boeva AU - Gudrun Schleiermacher AU - Olivier Delattre AU - Isabelle Janoueix-Lerosey Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/23/2021.01.07.425710.abstract N2 - 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. Here, we demonstrate that the knock-out of GATA3, but not of PHOX2A or PHOX2B, in noradrenergic cells induces a mesenchymal phenotype. Our results document spontaneous plasticity in several models between both identities and show that plasticity relies on epigenetic reprogramming. We demonstrate that an in vivo microenvironment provides a powerful pressure towards a noradrenergic identity for these models. Consistently, tumor cells with a mesenchymal identity are not detected in a series of PDX models. Further study of the intra-tumor noradrenergic heterogeneity reveals two distinct cell populations exhibiting features of chromaffin-like or sympathoblast-like cells. This work emphasizes that both external cues of the environment and intrinsic factors control plasticity and cell identity in neuroblastoma.Competing Interest StatementThe authors have declared no competing interest. ER -