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| Home > Publications database > H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model. > print |
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| 001 | 167358 | ||
| 005 | 20240229133538.0 | ||
| 024 | 7 | _ | |a 10.1016/j.ccell.2021.01.005 |2 doi |
| 024 | 7 | _ | |a pmid:33545065 |2 pmid |
| 024 | 7 | _ | |a 1535-6108 |2 ISSN |
| 024 | 7 | _ | |a 1878-3686 |2 ISSN |
| 024 | 7 | _ | |a altmetric:99418713 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2021-00304 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Haag, Daniel |0 P:(DE-He78)4e91a6c1d8301c9e964b25e084804264 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model. |
| 260 | _ | _ | |a New York, NY |c 2021 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1615467292_10451 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:B062#LA:B062#2021 Mar 8;39(3):407-422.e13 |
| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a DIPG |2 Other |
| 650 | _ | 7 | |a H3.3-K27M |2 Other |
| 650 | _ | 7 | |a H3K27me3 |2 Other |
| 650 | _ | 7 | |a H3K4me3 |2 Other |
| 650 | _ | 7 | |a NSC |2 Other |
| 650 | _ | 7 | |a OPC |2 Other |
| 650 | _ | 7 | |a bivalent chromatin |2 Other |
| 650 | _ | 7 | |a glioma |2 Other |
| 650 | _ | 7 | |a iPSC |2 Other |
| 650 | _ | 7 | |a orthotopic xenograft |2 Other |
| 700 | 1 | _ | |a Mack, Norman |0 P:(DE-He78)e73a0a4fab40344d89d693cbe1df3109 |b 1 |u dkfz |
| 700 | 1 | _ | |a Benites Goncalves da Silva, Patricia |0 P:(DE-He78)3c0df100616117ded2bf0f9cc3133de7 |b 2 |u dkfz |
| 700 | 1 | _ | |a Statz, Britta |0 P:(DE-He78)5f5223d7faa01a1e1df8a30d85cff5b0 |b 3 |u dkfz |
| 700 | 1 | _ | |a Clark, Jessica |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Tanabe, Koji |b 5 |
| 700 | 1 | _ | |a Sharma, Tanvi |0 P:(DE-He78)36e1ec4777d5b7887344177dca41eae9 |b 6 |u dkfz |
| 700 | 1 | _ | |a Jäger, Natalie |0 P:(DE-He78)bff9e3e3d86865d2b0836bb8f3ce98f3 |b 7 |u dkfz |
| 700 | 1 | _ | |a Jones, David T W |0 P:(DE-He78)551bb92841f634070997aa168d818492 |b 8 |u dkfz |
| 700 | 1 | _ | |a Kawauchi, Daisuke |0 P:(DE-He78)0ac2bd1a9fb1823a351ee4434d80808b |b 9 |u dkfz |
| 700 | 1 | _ | |a Wernig, Marius |b 10 |
| 700 | 1 | _ | |a Pfister, Stefan |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 11 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1016/j.ccell.2021.01.005 |g p. S1535610821000490 |0 PERI:(DE-600)2074034-7 |n 3 |p 407-422.e13 |t Cancer cell |v 39 |y 2021 |x 1535-6108 |
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