Abstract B78: Role of noradrenergic core regulatory circuitry transcription factors in neuroblastoma cell identity

摘要: Introduction: The heterogeneity of neuroblastoma cell identity has been recently revealed with the characterization noradrenergic and NCC (neural crest cell)-like/mesenchymal cells, each type being governed by a core regulatory circuitry (CRC) specific transcription factors (Boeva et al., 2017; van Groningen 2017). Whereas CRC includes PHOX2B, HAND2, GATA3 factors, associated to NCC-like/mesenchymal is composed AP-1 among others. present study aims at deciphering role identity-related PHOX2B GATA3, in establishment maintenance identity. Experimental Procedures: Using CRISPR-Cas9 gene editing approach, we performed knockout genes SH-SY5Y line. obtained clones were characterized terms growth, phenotype, identity, using particular transcriptomic (RNA-seq) epigenomic (H3K27ac ChIP-seq) analysis. Results:PHOX2B line did not change its PHOX2B−/− cells keep their demonstrating that expression essential for CRC. Nevertheless, absence these decreased proliferation both vitro vivo, after mouse xenografts. In contrast exhibit mesenchymal phenotype: GATA3−/− harbor actin stress fibers display migration invasion capacities. Compared parental they higher resistance chemotherapy vitro. hierarchical unsupervised clustering, show profile close lines, weak set including high related Consistently profile, are super-enhancer landscape SH-EP Finally, vivo xenograft experiments. Further experiments ongoing explore tumors. Conclusions: which two members CRC, play different roles cells. We hypothesize PHOX2A could compensate thus explaining why maintain contrast, Bioinformatics analyses decipher reprogramming process Citation Format: Agathe Peltier, Caroline Louis-Brennetot, Cecile Pierre-Eugene, Thirant, Simon Durand, Divya Sahu, Sandrine Grossetete-Lalami, Virginie Raynal, Sylvain Baulande, Olivier Delattre, Valentina Boeva, Isabelle Janoueix-Lerosey. Role [abstract]. In: Proceedings AACR Special Conference on Advances Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Res 2020;80(14 Suppl):Abstract nr B78.