Lineage tracing of soma-to-primordial germ cell-like conversion in human tumor cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE330850 | GEO | 2026/05/13
REPOSITORIES: GEO
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Project description:As germ cell precursor, primordial germ cells (PGCs) are widely used in transgenic animal production, regenerative medicine and other fields. However, the regulation mechanism of chicken PGCs is not incomplete, which leads to the insufficient amount of chicken PGCs obtained in vitro, which seriously affects the specific application of PGCs. During PGC formation (differentiation from ESCs to PGCs), some proteins have inconsistent changes in transcription level and protein abundance. Mediating proteasome degradation is one of the most important roles of protein ubiquitination, and enrichment analysis of transcriptome and proteome also suggests an important role of ubiquitination in the process of PGCs. In order to explore the important functions and potential targets of ubiquitination, we collected chicken ESCs and PGCs cells for label free ubiquitomics analysis. This study preliminarily analyzed how ubiquitination regulates the formation of chicken PGCs, providing a theoretical basis for the subsequent research and specific application of PGCs.
2025-09-08 | PXD052543 | Pride
Project description:The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast. Induction requires BMP4 signalling to prospective PGCs and the intrinsic action of PGC transcription factors (TFs). However, the molecular mechanisms connecting BMP4 action to induction of PGC TFs that are responsible for segregation of PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Down-regulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro dramatically increases PGCLC differentiation efficiency and prolongs the period of PGC competence. In the absence of Otx2 activity, PGCLC differentiation becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC TF Blimp1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that Otx2 acts repressively upstream of PGC TFs and functions as a roadblock to prevent the untimely entry of pluripotent stem cells into the PGC lineage, thereby ensuring correct spatio-temporal segregation of the germline and soma.
2018-07-06 | GSE116640 | GEO
Project description:Rabbit embryos, as in humans, develop as bilaminar discs at gastrulation and unlike egg cylinders as in rodents. Mammalian primordial germ cells (PGCs) in all species originate during gastrulation. We sequence the transcriptomes of rabbit embryos during gastrulation, and show that rabbit PGC (rbPGC) specification occurs at the posterior epiblast at the onset of gastrulation
2021-10-14 | E-MTAB-10893 | biostudies-arrayexpress
Project description:MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that the number of primordial germ cells (PGCs) decreased dramatically after MCM8 deficiency due to proliferation defects. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9 in PGCs, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results suggest that MCM8 interacts with R-loop-resolving factors to prevent DNA damage in PGCs, thus maintaining PGC proliferation and establishing the reproductive reserve. Our findings thus reveal a novel role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.
2024-05-31 | PXD050727 | Pride
Project description:Rabbit embryos, as in humans, develop as bilaminar discs at gastrulation and unlike egg cylinders as in rodents. Mammalian primordial germ cells (PGCs) in all species originate during gastrulation. We sequence the transcriptomes of rabbit embryos during gastrulation, and show that rabbit PGC (rbPGC) specification occurs at the posterior epiblast at the onset of gastrulation
2021-10-14 | E-MTAB-10892 | biostudies-arrayexpress
Project description:Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is known about the properties of PGCs at the metabolite and protein levels, which are directly responsible for the control of cell function. Here, we report the metabolic profiles of PGCs through the first comprehensive analyses of the metabolome and proteome, including remarkable activation of oxidative phosphorylation in mitochondria. Moreover, conversion of energy metabolism is involved in the control of PGC reprogramming and differentiation of pluripotential stem cells (PSCs) into PGCs in culture. Our findings about the unique metabolic property of PGCs provide novel insights into our understanding of the importance of distinct energy metabolism for switching PGC and PSC status.
2018-12-31 | GSE89738 | GEO
Project description:Rabbit embryos, as in humans, develop as bilaminar discs at gastrulation and unlike egg cylinders as in rodents. Mammalian primordial germ cells (PGCs) in all species originate during gastrulation. We sequence the transcriptomes of rabbit embryos during gastrulation, and show that rabbit PGC (rbPGC) specification occurs at the posterior epiblast at the onset of gastrulation
2021-10-14 | E-MTAB-10894 | biostudies-arrayexpress
Project description:Background: During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells. Results: We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein, Smaug, is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding-proteins function independently to control transcript elimination. Conclusion: The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance. There are 26 samples in total, including 1-to-3 hour, 3-to-5 hour, 5-to-7 hour PGCs in wild type and smaug mutant flies and 1-to-3 hour somatic cells in wild type flies. Except for the 1-to-3 hour and 3-to-5 hour smaug mutant PGCs which have three replicates, all the other samples have four replicates.
2012-02-08 | E-GEOD-34397 | biostudies-arrayexpress
Project description:In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment1. In female PGCs, expression of Stimulated by retinoic acid 8 (Stra8) and meiosis are induced in response to retinoic acid (RA) provided by the mesonephroi2-4. Given the widespread role of RA signaling during development8,9, the molecular mechanism specifying the competence of PGCs to timely express Stra8 and enter meiosis are unknown2,10. Here we identify gene dosage dependent roles in PGC development for Ring1 and Rnf2, two central components of the Polycomb Repressive Complex 1 (PRC1)11,13. Both paralogs are essential for PGC development between day 10.5 and 11.5 of gestation. Rnf2 is subsequently required in female PGCs for maintaining high levels of Oct4 and Nanog expression6, and for preventing premature induction of meiotic gene expression and entry into meiotic prophase. Chemical inhibition of RA signaling partially suppresses precocious Oct4 down-regulation and Stra8 activation in Rnf2-deficient female PGCs. Chromatin immunoprecipitation analyses show that Stra8 is a direct target of PRC1 and PRC2 in PGCs. These data demonstrate the importance of PRC1 gene dosage in PGC development and in coordinating the timing of sex differentiation of female PGCs by antagonizing extrinsic RA signaling. Gene expression of mouse primordial germ cells was analysed using Affymetrix microarray. Primodial germ cells were purified from embryos carrying Oct4(deltaPE)-GFP transgene by FACS.
2013-03-14 | E-GEOD-42782 | biostudies-arrayexpress
Project description:Background: During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells. Results: We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein, Smaug, is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding-proteins function independently to control transcript elimination. Conclusion: The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance.
2012-02-08 | GSE34397 | GEO