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@ARTICLE{Graf:179252,
author = {M. Graf and M. Interlandi and N. Moreno and D. Holdhof and
C. Göbel and V. Melcher and J. Mertins and T. K. Albert and
D. Kastrati and A. Alfert and T. Holsten and F. de Faria and
M. Meisterernst and C. Rossig and M. Warmuth-Metz and J.
Nowak and G. Meyer Zu Hörste and C. Mayère and S. Nef and
P. Johann$^*$ and M. C. Frühwald and M. Dugas and U.
Schüller and K. Kerl},
title = {{S}ingle-cell transcriptomics identifies potential cells of
origin of {MYC} rhabdoid tumors.},
journal = {Nature Communications},
volume = {13},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2022-00534},
pages = {1544},
year = {2022},
abstract = {Rhabdoid tumors (RT) are rare and highly aggressive
pediatric neoplasms. Their epigenetically-driven
intertumoral heterogeneity is well described; however, the
cellular origin of RT remains an enigma. Here, we establish
and characterize different genetically engineered mouse
models driven under the control of distinct promoters and
being active in early progenitor cell types with diverse
embryonic onsets. From all models only Sox2-positive
progenitor cells give rise to murine RT. Using single-cell
analyses, we identify distinct cells of origin for the SHH
and MYC subgroups of RT, rooting in early stages of
embryogenesis. Intra- and extracranial MYC tumors harbor
common genetic programs and potentially originate from fetal
primordial germ cells (PGCs). Using PGC specific Smarcb1
knockout mouse models we validate that MYC RT originate from
these progenitor cells. We uncover an epigenetic imbalance
in MYC tumors compared to PGCs being sustained by
epigenetically-driven subpopulations. Importantly,
treatments with the DNA demethylating agent decitabine
successfully impair tumor growth in vitro and in vivo. In
summary, our work sheds light on the origin of RT and
supports the clinical relevance of DNA methyltransferase
inhibitors against this disease.},
cin = {B062 / HD01},
ddc = {500},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35318328},
doi = {10.1038/s41467-022-29152-4},
url = {https://inrepo02.dkfz.de/record/179252},
}