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Series GSE149499 Query DataSets for GSE149499
Status Public on Jul 20, 2021
Title DMRT1-mediated reprogramming drives development of cancer resembling human germ cell tumors with features of totipotency
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary In vivo reprogramming provokes a wide range of cell fate conversion. Here, we discover that in vivo induction of higher levels of OSKM in mouse somatic cells leads to increased expression of primordial germ cell (PGC)-related genes and provokes genome-wide erasure of genomic imprinting, which takes place exclusively in PGCs. Moreover, the in vivo OSKM reprogramming results in development of cancer that resembles human germ cell tumors. Like a subgroup of germ cell tumors, propagated tumor cells differentiate into trophoblasts. Moreover, these tumor cells give rise to induced pluripotent stem cells (iPSCs) with expanded differentiation potential into trophoblasts. Remarkably, the tumor-derived iPSCs are able to contribute to non-neoplastic somatic cells in adult mice. Mechanistically, DMRT1, which is expressed in PGCs, drives the reprogramming and propagation of the tumor cells in vivo. Furthermore, the DMRT1-related epigenetic landscape is associated with trophoblast competence of the reprogrammed cells and provides a therapeutic target for germ cell tumors. These results reveal an unappreciated route for somatic cell reprogramming and underscore the impact of reprogramming in development of germ cell tumors.
 
Overall design Analyzing transcriptional profiles and DNA methylation profiles by RNA-seq, WGBS and Methyl-seq in OSKM-induced cellular reprogramming in vitro and in vivo
 
Contributor(s) Kabata M, Yamamoto T, Yamada Y
Citation(s) 34413299
Submission date Apr 28, 2020
Last update date Sep 29, 2021
Contact name Yasuhiro Yamada
E-mail(s) yasu@ims.u-tokyo.ac.jp
Organization name University of Tokyo
Department Institute of Medical Science
Lab Division of Stem Cell Pathology
Street address 4-6-1, Shirokanedai, Minato-ku
City Tokyo
ZIP/Postal code 108-8639
Country Japan
 
Platforms (3)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (70)
GSM4503923 RNAseq KH2 LacZ ESCs
GSM4503924 RNAseq S-iPSCs-1-1 Passage4
GSM4503925 RNAseq S-iPSCs-2-1 Passage4
Relations
BioProject PRJNA628924
SRA SRP258895

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE149499_1.TPM_D-OSKM_iPSCs_.xlsx 3.1 Mb (ftp)(http) XLSX
GSE149499_2.TPM_Kidney_tumor_.xlsx 5.6 Mb (ftp)(http) XLSX
GSE149499_3.TPM_in_vitro_.xlsx 5.3 Mb (ftp)(http) XLSX
GSE149499_4.TPM_in_vivo_.xlsx 30.0 Mb (ftp)(http) XLSX
GSE149499_RAW.tar 1.1 Gb (http)(custom) TAR (of BEDGRAPH, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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