TY - JOUR A1 - Sriha, Jessica A1 - Louis-Brennetot, Caroline A1 - Pierre-Eugène, Cécile A1 - Baulande, Sylvain A1 - Raynal, Virginie A1 - Kramdi, Amira A1 - Adameyko, Igor A1 - Ernsberger, Uwe A1 - Deller, Thomas A1 - Delattre, Olivier A1 - Janoueix-Lerosey, Isabelle A1 - Rohrer, Hermann T1 - BET and CDK inhibition reveal differences in the proliferation control of sympathetic ganglion neuroblasts and adrenal chromaffin cells T2 - Cancers N2 - Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal. KW - chromaffin cell KW - sympathetic KW - neuroblast KW - bromodomain and extraterminal (BET) protein KW - transcriptional cyclin-dependent kinase Y1 - 2022 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73499 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-734999 SN - 2072-6694 N1 - Funding: Wilhelm Sander Stiftung (H.R.; grant 2018-042.1); Mayent-Rothschild Foundation and INCa (H.R.). High-throughput sequencing was performed using the ICGex NGS platform of the Institut Curie supported by the grants ANR-10-EQPX-03 (Equipex) and ANR-10-INBS-09-08 (France Génomique Consortium) from the Agence Nationale de la Recherche ("Investissements d’Avenir" program), by the ITMO-Cancer Aviesan (Plan Cancer III), and by the SiRIC-Curie program (SiRIC Grant INCa-DGOS-465 and INCa-DGOSInserm_12554). The Delattre and Adameyko teams are supported by the ERC Synergy program "Kill-or-differentiate". N1 - Raw data for RNA-seq are available in the Gene Expression Omnibus (GEO) under the accession number GSE200379 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200379). VL - 14 IS - 11, art. 2755 SP - 1 EP - 21 PB - MDPI CY - Basel ER -