Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries
Nature Genetics 49, 1408 (2017).
doi:10.1038/ng.3921
Authors: Valentina Boeva, Caroline Louis-Brennetot, Agathe Peltier, Simon Durand, Cécile Pierre-Eugène, Virginie Raynal, Heather C Etchevers, Sophie Thomas, Alban Lermine, Estelle Daudigeos-Dubus, Birgit Geoerger, Martin F Orth, Thomas G P Grünewald, Elise Diaz, Bertrand Ducos, Didier Surdez, Angel M Carcaboso, Irina Medvedeva, Thomas Deller, Valérie Combaret, Eve Lapouble, Gaelle Pierron, Sandrine Grossetête-Lalami, Sylvain Baulande, Gudrun Schleiermacher, Emmanuel Barillot, Hermann Rohrer, Olivier Delattre & Isabelle Janoueix-Lerosey
Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on P...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Valentina Boeva Caroline Louis-Brennetot Agathe Peltier Simon Durand C é cile Pierre-Eug è ne Virginie Raynal Heather C Etchevers Sophie Thomas Alban Lermine Estelle Daudigeos-Dubus Birgit Geoerger Martin F Orth Thomas G P Gr ü newald Elise Diaz Bertra Tags: Letter Source Type: research
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