RT Journal Article
SR Electronic
T1 Interplay between intrinsic reprogramming potential and microenvironment controls neuroblastoma cell plasticity and identity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.07.425710
DO 10.1101/2021.01.07.425710
A1 Cécile Thirant
A1 Agathe Peltier
A1 Simon Durand
A1 Amira Kramdi
A1 Caroline Louis-Brennetot
A1 Cécile Pierre-Eugène
A1 Ana Costa
A1 Amandine Grelier
A1 Sakina Zaïdi
A1 Nadège Gruel
A1 Irène Jimenez
A1 Eve Lapouble
A1 Gaëlle Pierron
A1 Hervé J. Brisse
A1 Arnaud Gauthier
A1 Paul Fréneaux
A1 Sandrine Grossetête-Lalami
A1 Laura G. Baudrin
A1 Virginie Raynal
A1 Sylvain Baulande
A1 Angela Bellini
A1 Jaydutt Bhalshankar
A1 Angel M. Carcaboso
A1 Birgit Geoerger
A1 Hermann Rohrer
A1 Didier Surdez
A1 Valentina Boeva
A1 Gudrun Schleiermacher
A1 Olivier Delattre
A1 Isabelle Janoueix-Lerosey
YR 2021
UL http://biorxiv.org/content/early/2021/03/23/2021.01.07.425710.abstract
AB 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.