dc.contributor.author | Saldana-Guerrero, IM | |
dc.contributor.author | Montano-Gutierrez, LF | |
dc.contributor.author | Boswell, K | |
dc.contributor.author | Hafemeister, C | |
dc.contributor.author | Poon, E | |
dc.contributor.author | Shaw, LE | |
dc.contributor.author | Stavish, D | |
dc.contributor.author | Lea, RA | |
dc.contributor.author | Wernig-Zorc, S | |
dc.contributor.author | Bozsaky, E | |
dc.contributor.author | Fetahu, IS | |
dc.contributor.author | Zoescher, P | |
dc.contributor.author | Pötschger, U | |
dc.contributor.author | Bernkopf, M | |
dc.contributor.author | Wenninger-Weinzierl, A | |
dc.contributor.author | Sturtzel, C | |
dc.contributor.author | Souilhol, C | |
dc.contributor.author | Tarelli, S | |
dc.contributor.author | Shoeb, MR | |
dc.contributor.author | Bozatzi, P | |
dc.contributor.author | Rados, M | |
dc.contributor.author | Guarini, M | |
dc.contributor.author | Buri, MC | |
dc.contributor.author | Weninger, W | |
dc.contributor.author | Putz, EM | |
dc.contributor.author | Huang, M | |
dc.contributor.author | Ladenstein, R | |
dc.contributor.author | Andrews, PW | |
dc.contributor.author | Barbaric, I | |
dc.contributor.author | Cresswell, GD | |
dc.contributor.author | Bryant, HE | |
dc.contributor.author | Distel, M | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Taschner-Mandl, S | |
dc.contributor.author | Farlik, M | |
dc.contributor.author | Tsakiridis, A | |
dc.contributor.author | Halbritter, F | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-07-30T13:57:11Z | |
dc.date.available | 2024-07-30T13:57:11Z | |
dc.date.issued | 2024-05-03 | |
dc.identifier | ARTN 3745 | |
dc.identifier | 10.1038/s41467-024-47945-7 | |
dc.identifier.citation | Nature Communications, 2024, 15 (1), pp. 3745 - | en_US |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6321 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-024-47945-7 | |
dc.identifier.doi | 10.1038/s41467-024-47945-7 | |
dc.description.abstract | Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours. | |
dc.format | Electronic | |
dc.format.extent | 3745 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | NATURE PORTFOLIO | en_US |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Humans | |
dc.subject | Neuroblastoma | |
dc.subject | Neural Crest | |
dc.subject | Female | |
dc.subject | DNA Copy Number Variations | |
dc.subject | Cell Differentiation | |
dc.subject | N-Myc Proto-Oncogene Protein | |
dc.subject | Chromosome Aberrations | |
dc.subject | Human Embryonic Stem Cells | |
dc.subject | Transcriptome | |
dc.subject | Cell Line, Tumor | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.title | A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-04-15 | |
dc.date.updated | 2024-07-30T13:56:00Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s41467-024-47945-7 | en_US |
rioxxterms.licenseref.startdate | 2024-05-03 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38702304 | |
pubs.issue | 1 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-024-47945-7 | |
pubs.volume | 15 | |
icr.researchteam | Paediatric Tumour Biology | en_US |
dc.contributor.icrauthor | Poon, Evon | |
dc.contributor.icrauthor | Chesler, Louis | |
icr.provenance | Deposited by Mr Arek Surman on 2024-07-30. Deposit type is initial. No. of files: 1. Files: s41467-024-47945-7.pdf | |