| Online-Ressource |
Verfasst von: | Haag, Daniel [VerfasserIn]  |
| Mack, Norman [VerfasserIn]  |
| Benites Goncalves da Silva, Patricia [VerfasserIn]  |
| Statz, Britta [VerfasserIn]  |
| Clark, Jessica [VerfasserIn]  |
| Tanabe, Koji [VerfasserIn]  |
| Sharma, Tanvi [VerfasserIn]  |
| Jäger, Natalie [VerfasserIn]  |
| Jones, David T. W. [VerfasserIn]  |
| Kawauchi, Daisuke [VerfasserIn]  |
| Wernig, Marius [VerfasserIn]  |
| Pfister, Stefan [VerfasserIn]  |
Titel: | H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model |
Verf.angabe: | Daniel Haag, Norman Mack, Patricia Benites Goncalves da Silva, Britta Statz, Jessica Clark, Koji Tanabe, Tanvi Sharma, Natalie Jäger, David T.W. Jones, Daisuke Kawauchi, Marius Wernig, and Stefan M. Pfister |
E-Jahr: | 2021 |
Jahr: | 4 February 2021 |
Umfang: | 29 S. |
Fussnoten: | Gesehen am 05.02.2021 |
Titel Quelle: | Enthalten in: Cancer cell |
Ort Quelle: | Cambridge, Mass. : Cell Press, 2002 |
Jahr Quelle: | 2021 |
Band/Heft Quelle: | 39(2021), 3, Seite 407-422.e13 |
ISSN Quelle: | 1878-3686 |
Abstract: | Diffuse intrinsic pontine glioma (DIPG) is an aggressive childhood tumor of the brainstem with currently no curative treatment available. The vast majority of DIPGs carry a histone H3 mutation leading to a lysine 27-to-methionine exchange (H3K27M). We engineered human induced pluripotent stem cells (iPSCs) to carry an inducible H3.3-K27M allele in the endogenous locus and studied the effects of the mutation in different disease-relevant neural cell types. H3.3-K27M upregulated bivalent promoter-associated developmental genes, producing diverse outcomes in different cell types. While being fatal for iPSCs, H3.3-K27M increased proliferation in neural stem cells (NSCs) and to a lesser extent in oligodendrocyte progenitor cells (OPCs). Only NSCs gave rise to tumors upon induction of H3.3-K27M and TP53 inactivation in an orthotopic xenograft model recapitulating human DIPGs. In NSCs, H3.3-K27M leads to maintained expression of stemness and proliferative genes and a premature activation of OPC programs that together may cause tumor initiation. |
DOI: | doi:10.1016/j.ccell.2021.01.005 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1016/j.ccell.2021.01.005 |
| Volltext: https://www.sciencedirect.com/science/article/pii/S1535610821000490 |
| DOI: https://doi.org/10.1016/j.ccell.2021.01.005 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | bivalent chromatin |
| DIPG |
| glioma |
| H3.3-K27M |
| H3K27me3 |
| H3K4me3 |
| iPSC |
| NSC |
| OPC |
| orthotopic xenograft |
K10plus-PPN: | 1747449784 |
Verknüpfungen: | → Zeitschrift |
H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model / Haag, Daniel [VerfasserIn]; 4 February 2021 (Online-Ressource)