Teratoma development in adult mice from extending pluripotency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA879199 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21524849_1.fastq.gz | Fastqsanger.gz | |||
| SRR21524849_2.fastq.gz | Fastqsanger.gz | |||
| SRR21524850_1.fastq.gz | Fastqsanger.gz | |||
| SRR21524850_2.fastq.gz | Fastqsanger.gz | |||
| SRR21524851_1.fastq.gz | Fastqsanger.gz |
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Project description:Embryonic stem cells (ESCs) have practically unlimited proliferation capacity and unrivalled differentiation potential, thus providing an attractive source of cells for regenerative medicine. Numerous ESC culture systems have been established to achieve extended pluripotency. However, long-term safety evaluation on these extended pluripotent state cells (EPS) were largely overlooked. Here, we generate full ESC-mice through tetraploid embryo complementation assay from the prevailing extended pluripotent stem cells. Two years of safety evaluation show that all the EPS mice developed late onset retroperitoneal teratomas whereas no abnormality was observed in the conventional ESC mice. Whole exome sequencing and chromatin accessibility analysis on the EPS and the corresponding tumor tissues identify the global chromatin reconfiguration but only minor genetic variation in EPS. Correspondingly, the teratomas could be attributed to a proportion of undifferentiated cells from extended pluripotency. Our study uncovers the prevailing late onset tumorigenesis in EPS-mouse, highlighting the impact of early epigenetic variations on tumorigenicity in the adult.
2022-09-24 | GSE213109 | GEO
Project description:The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
2009-02-01 | GSE12499 | GEO
Project description:Studying early human developmental processes requires access to a model system that is easy to perturb, either genetically or chemically, genetically tractable and recapitulates key features of organogenesis. We propose that the teratoma, a recognized standardused for for validating pluripotency in stem cells, could be a promising platform for modeling human development. Teratomas differentiate to all germ layers, have regions of complex tissue-like organization with internal vasculature, and are relatively easy to generate and thus accessible, especially in comparison to human fetal tissue. Teratomas, however, have not been characterized rigorously to determine their suitability to model human developmental processes the diversity and identities of the cell types present, and their level of maturity in comparison to human developmental cell types. We thus systematically analyzed, perturbed, and engineered human pluripotent stem cell (PSC)-derived teratomas. Usingused histology, RNA in situ hybridization, and single cell RNA-seq (scRNA-seq) of 179,632 cells across 23 teratomas generated from 4 cell lines, we observed to find that teratomas reproducibly contain approximatelyat least 20 cell types across all three germ layers, and the cell type heterogeneity between teratomas was comparable to that found in organoid systems. We found that a significant fraction of injected PSCs engrafted, suggestingused lentiviral barcoding to determine there is minimalno bottlenecking during teratoma formation. Additionally, we mapped our teratoma data to published human fetal data and showed that the teratoma gut and brain cell types correspond well to existing fetal gut and brain scRNA-seq datasetscells. We then performed a CRISPR-Cas9 knockout screen in teratomas targeting key genes known to be embryonic lethal, and found that TWIST1, RUNX1, ASCL1, CDX2, and KLF6 knockouts resulted in assessed shifts in lineage abundance. using scRNA-seq. We found that TWIST1, RUNX1, ASCL1, CDX2, and KLF6 knockouts resulted in reproducible shifts in lineage abundance consistent with known biology. All of these These knockouts had effects on cell types from multiple germ layers, showing that the teratoma can serve as a platform to studymodel all major human lineages of human development simultaneously. Additionally, we ran a CRISPR-Cas9 screen targetingWe also knocked out the genes underlying Rett, Pitt-Hopkins, and L1 Syndromes and identified cell type specific shifts in gene expression. Finally, we engineered a novel miRNA-regulated suicide gene circuit that enriches for tissues in the teratoma that express a specific miRNA that selectively depletes cells that do not express a tissue-specific endogenous miRNA, allowing us to enrich for desired lineages in the teratoma, which we demonstrated using miR-124 to enrich for neuro-ectoderm. Specifically, we used miR-124 to successfully enrich for neuro-ectoderm. Taken together, we believe the teratoma is a promising platform for modeling multi-lineage human development, functional genetic screening, and cellular engineering
2020-11-04 | GSE156170 | GEO
Project description:Human induced pluripotent stem (iPS) cells are capable of differentiating into derivatives of the three embryonic germ layers both in vitro and in vivo. To date the the molecular differences between teratoma-forming cells and non-teratoma-forming cells has not been analysed. A cell line, B1, bears typical ES cell-like morphology, expression of pluripotency-associated genes, and in vitro pluripotency capacity, but fails to form teratomas after subcutaneously injected into immune-deficient mice based on histological analysis. Besides histological analysis, we characterized the tumors derived from line B1, and teratomas derived from bona fida iPS and ES (line H1) cells respectively, using microarray-based gene expression analysis. The expression levels of pluripotency-associated markers in B1 cells were comparable to that in iPS and ES cells, while the complexity of tissue expression commitment was decreased upon spontaneous differentiation of B1 cells as compared to iPS and ES cells. Total RNA obtained from HFF1 (human foreskin fibroblast) cells, line B1, iPS-A4, iPS-B4 and ES (line H1) cells, and their derived tumors in immune-deficient mice.
2012-04-29 | E-GEOD-31970 | biostudies-arrayexpress
Project description:Human induced pluripotent stem (iPS) cells are capable of differentiating into derivatives of the three embryonic germ layers both in vitro and in vivo. To date the the molecular differences between teratoma-forming cells and non-teratoma-forming cells has not been analysed. A cell line, B1, bears typical ES cell-like morphology, expression of pluripotency-associated genes, and in vitro pluripotency capacity, but fails to form teratomas after subcutaneously injected into immune-deficient mice based on histological analysis. Besides histological analysis, we characterized the tumors derived from line B1, and teratomas derived from bona fida iPS and ES (line H1) cells respectively, using microarray-based gene expression analysis. The expression levels of pluripotency-associated markers in B1 cells were comparable to that in iPS and ES cells, while the complexity of tissue expression commitment was decreased upon spontaneous differentiation of B1 cells as compared to iPS and ES cells.
2012-04-30 | GSE31970 | GEO
Project description:In germ cell tumors (GCT), a growing mature teratoma during or after chemotherapy with decreasing tumor markers is defined as ´growing teratoma syndrome` (GTS) according to its first describer Logothetis et al. in 1982. Due to the small number of available cases worldwide, not much is known about this continuously growing tumor and its pathogenesis. Especially in cases with extensive and surgical uncontrollable tumor mass, specific therapeutic options and biomarkers early indicating presence of GTS are still lacking. In this study, GTS was stratified into a slow (< 0.5 cm / month), medium (0.5 – 1.5 cm / month) and rapid (> 1.5 cm / month) group based on the tumor growth rate. We analyzed the secretome of 3 GTS samples of each subgroup and 3 teratomas. The secreted proteins were isolated from ex vivo cultivated tissues and analyzed by liquid-chromatography coupled to mass spectrometry (LS-MS).
2024-11-15 | PXD043529 | Pride
Project description:Defining the Teratoma as a Model for Multi-Lineage Human Development
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Project description:expression analysis of teratoma, grown from mouse embryonic stem cells that are Evi/Wls knockout cells and comparison with wildtype (control) tumors
2014-12-10 | E-MTAB-2927 | biostudies-arrayexpress
Project description:MicroRNA sequencing of slow and rapid growing teratoma. Teratoma without a growth trend were included as controls. In total, 9 samples were analyzed for their expressed microRNAs by sequencing. YST and EC tissues were identified from the biobank of the Department of Urology (University Hospital Düsseldorf). Total RNA has been isolated and subsequently microRNA sequencing has been performed.
2024-04-28 | GSE251975 | GEO