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A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons

ABSTRACT: A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons

PROVIDER: PRJNA576722 | ENA |

REPOSITORIES: ENA

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A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [RNA-seq]

Project description:PRDM14 is a crucial regulator of mouse primordial germ cells (mPGC), epigenetic reprogramming and pluripotency, but its role in the evolutionarily divergent regulatory network of human PGCs (hPGCs) remains unclear. Besides, a previous knockdown study indicated that PRDM14 might be dispensable for human germ cell fate. Here, we decided to use inducible degrons for a more rapid and comprehensive PRDM14 depletion. We show that PRDM14 loss results in significantly reduced specification efficiency and an aberrant transcriptome of human PGC-like cells (hPGCLCs) obtained in vitro from human embryonic stem cells (hESCs). Chromatin immunoprecipitation and transcriptomic analyses suggest that PRDM14 cooperates with TFAP2C and BLIMP1 to upregulate germ cell and pluripotency genes, while repressing WNT signalling and somatic markers. Notably, PRDM14 targets are not conserved between mouse and human, emphasising the divergent molecular mechanisms of PGC specification. The effectiveness of degrons for acute protein depletion is widely applicable in various developmental contexts.

2019-12-08 | GSE138673 | GEO

A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [ChIP-seq]

2019-12-08 | GSE138674 | GEO

A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [ChIP-seq]

Project description:A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [ChIP-seq]

| PRJNA576728 | ENA

A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [RNA-seq]

Project description:A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [RNA-seq]

| PRJNA576723 | ENA

A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons.

Project description: Not available

| S-EPMC7062732 | biostudies-literature

Single cell microarray analysis of mouse primordial germ cells with Prdm14 mutation.

Project description:Prdm14 is a critical gene for specifying mouse primordial germ cells (PGCs). The changes in expression in mouse PGCs caused by mutations of the Prdm14 gene were investigated at the single-cell level using microarray analysis.

2024-04-17 | GSE233342 | GEO

A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-08 | GSE138675 | GEO

Germline development in rat revealed by visualization and deletion of Prdm14

Project description:Primordial germ cells (PGCs), the founder cells of the germline, are specified in pre-gastrulating embryos in mammals, and subsequently migrate towards gonads to mature into functional gametes. Here, we investigated PGC development in rats, by genetically modifying Prdm14, a unique marker and a critical PGC transcriptional regulator. We trace PGC development in rats, for the first time, from specification until sex determination stage in fetal gonads using Prdm14 H2BVenus knock-in rats. We uncover that Prdm14’s crucial role in PGC specification is conserved between rat and mice, by analyzing Prdm14 deficient rat embryos. Notably, loss of Prdm14 completely abrogates the PGC program: failure in maintenance and/or activation of germ cell markers and pluripotency genes. Finally, we profile the transcriptome of the postimplantation epiblast and all PGC stages in rat, to reveal enrichment of distinct gene sets at each transition point, thereby providing an accurate transcriptional time-line for rat PGC development. Thus, the novel genetically modified rats and data sets obtained in this study will advance our knowledge on conserved vs species-specific features for germline development in mammals.

2019-12-26 | GSE135388 | GEO

SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

Project description:Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information. RNA-Seq analysis to investigate transcriptomes of hPGC-like cells (hPGCLCs), fetal hPGCs, TCam-2 and hESCs

2014-12-26 | E-GEOD-60138 | biostudies-arrayexpress

Expresssion data of Prdm14 KO ESCs expressing each orthologues.

Project description:Gene regulatory networks underlying cellular pluripotency are controlled by a core circuitry of transcription factors, including POU5F1 and NANOG in mammals. However, the evolutionary origin and transformation of pluripotency transcriptional networks have not been elucidated in deuterostomes. PR domain-containing protein 14 (PRDM14) is specifically expressed in pluripotent cells and germ cells, and is required for establishing embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. Here, we compared the functions and expression patterns of PRDM14 orthologues within deuterostomes. Amphioxus PRDM14, zebrafish PRDM14, and the combination of sea urchin PRDM14 and CBFA2T compensated for disruption of the mouse Prdm14 gene in terms of maintaining mouse ESC pluripotency. Interestingly, Prdm14 was expressed in motor neurons, but not in germ cells in amphioxus embryos as observed in zebrafish embryos. Therefore, our results suggest that the integration of the PRDM14–CBFA2T complex into the transcriptional network for pluripotency may be essential for stabilizing pluripotency during the early amniote development.

2019-01-29 | GSE112904 | GEO

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