Genome-wide maps of Tex10 and chromatin state in Day 2 primordial germ cell-like cells (PGCLCs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE180799 | GEO | 2023/06/14
REPOSITORIES: GEO
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Project description:Primordial Germ Cells (PGCs) are a rare population of cells specified early in embryonic development that give rise to gametes - sperm and egg cells. Current in vitro systems to derive PGC-like cells (PGCLCs) from pluripotent cells use large embryoid bodies, exposed to signalling cocktails, that do not recapitulate the native embryonic environment during PGC formation. Here we show that mouse gastruloids, three-dimensional in vitro models of gastrulation, generate a population of Gastruloid-derived PGC-like cells (Gld-PGCLCs) that resemble early PGCs in vivo. Importantly, the conserved organisation of mouse gastruloids leads to coordinated spatial and temporal localisation of Gld-PGCLCs relative to surrounding somatic cells, even in the absence of exogenous PGC-specific signalling or extraembryonic tissues. In gastruloids, self-organised interactions between cells and tissues, including the endodermal epithelium, enables the specification, migration, and subsequent maturation of a pool of Gld-PGCLCs. As such, mouse gastruloids represent a new source of PGCLCs in vitro and, due to their inherent co-development, serve as a novel model of dynamic PGC development within integrated tissue environments.
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Project description:Tex10 depletion compromises the PGCLC specification and spermatogenesis
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Project description:Colorectal cancer (CRC) has become a predominant cancer worldwide. In order to understand the process of carcinogenesis, an shRNA library screening is employed for searching candidate genes that promote proliferation in the CRC cell line HT29. The candidate genes overlapped with differentially expressed genes in 32 CRC tumor tissues in the GEO dataset GSE8671. The seventh-ranked TEX10 is upregulated in CRC and its knockdown decreased cell proliferation. The TEX10 high-expression group exhibits worse overall survival (P = 0.003) and progression-free survival (P < 0.001) than the TEX10 low-expression group. TEX10 depletion decreases the growth of CRC cells in vitro and in vivo. GSEA indicates that the NF-κB pathway is significantly enriched in the genes downregulated by TEX10 knockdown. Mechanistically, TEX10 interacts with p65 and increases its nuclear localization. TEX10 promotes p65 occupancy at gene promoters and regulates the expression of a subset of p65-targeted genes including TNFAIP8, SAT1 and IL6ST. Taken together, this study identifies that TEX10 promotes the proliferation of CRC cells in a p65-dependent manner. In addition, high TEX10 expression is associated with poor prognosis in CRC patients.
2020-10-05 | GSE147334 | GEO
Project description:Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, develop pre-meiotic germ cell characteristics, including X-reactivation, imprint erasure, and cyst formation. Upon transplantation under ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which, through in vitro maturation and fertilization, contribute to fertile offspring. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ-cell development in vitro. We performed expression analysis of female PGC-like cells [PGCLCs; day 3 (d3), day 6 (d6), and day 3 followed by day 6 in aggregation with female embryonic day (E) 12.5 gonadal somatic cells (d3ag6)] in comparison to in vivo embryonic PGCs (E12.5 female PGCs and E9.5 PGCs) and male d6 PGCLCs. PGCLCs were marked with fluorescence of Blimp1-mVenus, stella-ECFP transgenic reporters (BVSC). PGCs were marked with fluorescence of the stella-EGFP transgenic reporter.
2012-11-05 | E-GEOD-40716 | biostudies-arrayexpress
Project description:In vitro generation of germ cells from pluripotent stem cells (PSCs) can crucially impact future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell-like cells (PGCLCs) to produce fertile gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. Notably, rat PGCLCs transplanted into the seminiferous tubules of germline-less rats produce spermatids, leading to the birth of viable offspring. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis.
2022-03-05 | GSE178701 | GEO
Project description:The Ventx genes are a family of non-clustered homeobox transcription factors that confer a ventral phenotype on mesodermal cells in the Xenopus laevis embryo. Ventx genes are conserved in vertebrates, although they have been lost in rodents. We evaluated the expression of VENTX during differentiation of a human pluripotent stem cell (hPSC) line in which a GFP reporter marked the expression of VENTX (VENTXGFP/w), discovering that VENTX was expressed in a subset of early primordial germ cell-like cells (PGCLCs). We generated a dual reporter hPSC line in which mCHERRY marked the pluripotency gene OCT4 (VENTXGFP/wOCT42AmCHERRY/w), and further modified this to also create a VENTX knock out line by deleting the VENTX homeodomain (VENTXGFP/-OCT42AmCHERRY/w). Transcriptional profiling experiments revealed two populations of PGCLCs, those that co expressed VENTX and OCT4 (GFP+mCHERRY+) and those that were VENTX-OCT4+ (GFP-mCHERRY+). Our analyses showed that VENTX+ and VENTX- PGCLCs clustered together, and also failed to reveal transcriptional consequences of VENTX deletion on commitment to PGCLCs. Evaluation of public databases confirmed expression of VENTX in populations of PGCLCs derived by others and in primary human embryonic germ cell samples. These results identify VENTX as a new PGC-associated gene in humans, however it does not seem to be required for initial human PGC commitment.
2021-01-20 | GSE144500 | GEO
Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. Genome binding/occupancy profiling of Tex10 was performed in mouse embryonic stem cells by ChIP sequencing.
2015-05-07 | E-GEOD-66735 | biostudies-arrayexpress
Project description:Mammalian germ cells first establish as primordial germ cells (PGCs). There is an increasing demand to investigate the characteristics of human germ cells including PGCs. Recent studies have established the methodologies to derive human germ cells such as PGCs from human induced pluripotent cells (iPSCs). The in vitro-derived PGCs are referred to as PGC-like cells (PGCLCs) and exhibit the characteristics of the PGCs immediately after specification. Here we performed bulk RNA-sequencing (RNA-Seq) of PGCLCs and their parental iPSCs to characterize the expression signatures of human genes and transposable elements in PGCLCs in detail.
2022-03-08 | GSE167570 | GEO
Project description:The induction of the primordial germ-like cells (PGCLCs) from primate pluripotent stem cells (PSCs)provides a powerful system to study the cellular and molecular mechanism underlying germline specification, which are difficult to study in vivo. However a comprehensive single cell RNA sequencing(scRNA-seq) analysis of the developmental trajectory of PGCLCs differentiation that also dissects the required niche has not been achieved. Here, we applied the embryoid body (EB) differentiation system to induce PGCLCs specification from male and female monkey naïve-state PSCs and then performed high throughput scRNA-seq analysis of approximately 40000 of naïve cells and cells within EBs. We found that EBs provided a niche for PGCLCs differentiation by secreting growth factors critical for PGCLCs specification, such as BPM2, BMP4 and WNT3. Moreover, the developmental trajectory of PGCLCs was reconstituted and gene expression dynamics were revealed. Our study outlines the roadmap of PGCLCs specification from PSCs and provides insights that will improve the differentiation efficiency of PGCLCs from PSCs.
2021-12-31 | GSE139432 | GEO