Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-binding proteins DND1 and NANOS3 coordinately suppress SOX4 in processing bodies for restricting the entry of germ cell lineage

ABSTRACT: Specification of germ cell fate establishes the germline development during early embryogenesis, yet the underlying mechanisms remain largely unknown in humans. Here we focus on the functional roles of the RNA-binding protein (RBP) DND1 in human germline specification. We deleted the whole genomic region of DND1 in human embryonic stem cells (hESCs), based on which we generated human primordial germ cell-like cells (hPGCLCs). Interestingly, we discovered an increased percentage of hPGCLCs induced from DND1 deleted hESCs, suggesting that DND1 may restrict the specification of human germ cell lineage. Mechanistic investigation reveals that DND1 forms a complex with another RBP NANOS3, in which DND1 facilitates the binding of NANOS3 to their target mRNAs. Furthermore, by analyzing the mRNAs bound by DND1 and NANOS3, we identified SOX4 mRNAs as the key downstream factor for DND1 and NANOS3 complex to restrict the induction of hPGCLCs. Interestingly, DND1 and NANOS3 function in processing bodies (P-bodies) to repress the translation of SOX4 mRNAs, where NANOS3 bridges the interaction between DND1 and the translational repressor 4E-T. Altogether, these findings identify the RBPs DND1 and NANOS3 as “break system” to restrict the entry of germ cell fate in humans.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268946 | GEO | 2025/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Heading towards a dead end: the role of DND1 in germ line differentiation of human iPSCs

Project description:The DND microRNA-mediated repression inhibitor 1 (DND1) is a conserved RNA binding protein (RBP) and plays an important role in survival and maintenance of primordial germ cells (PGCs) and the development of the male germline in zebrafish and mice. It was shown to be expressed in human pluripotent stem cells (PSCs), PGCs, and spermatogonia, but little is known about its specific role in pluripotency and human germline development. Here we use CRISPR/Cas mediated knockout and PGC-like cell (PGCLC) differentiation in human iPSCs to analyse if DND1 (1) plays a role in maintaining pluripotency and (2) in specification of PGCLCs. We generated several clonal lines with biallelic loss of function mutations and analysed their potential to differentiate towards PGCLCs and their gene expression on RNA and protein level via bulk RNA sequencing and mass spectrometry. The generated knockout iPSCs showed no differences in pluripotency gene expression, proliferation nor trilineage differentiation potential, but yielded reduced numbers o PGCLCs compared to their parental iPSCs. RNAseq analysis in PGCLCs showed significantly reduced expression of genes associated with cellular developmental processes and cell differentiation in knockout cells, including known markers for PGCs (NANOS3, SOX17, PRDM1, EPCAM) and naïve pluripotency (TFCP2L, DNMT3L).

2021-12-10 | PXD023802 | Pride

Divergent roles of KLF4 and TFCP2L1 in ground-state naive pluripotency and human primordial germ cell development

Project description:During development, human primordial germ cells (hPGCs) transition through a transcriptional and epigenetic state similar to pre-implantation epiblast cells called naive ground-state pluripotency. Diagnostic transcription factors that define this state include TFAP2C, KLF4, and TFCP2L1, with TFAP2C necessary for both establishment of the naive-like state in hPGC-like cells (hPGCLCs) as well as establishment and self-renewal of naive human embryonic stem cells (hESCs). Here, we show that KLF4 and TFCP2L1 are not required for hPGC specification or establishment of the naive-like state in hPGCLCs. Instead, KLF4 and TFCP2L1 are each required for reversion of primed hESCs to the self-renewing naive ground state. Additionally, TFCP2L1 but not KLF4 function after hPGC specification in the proliferation of the hPGCLC population.

2022-04-30 | GSE148717 | GEO

An ExtendedCulture System that Supports Human Primordial Germ Cell-Like Cells Survival and Initiation of DNA Methylation Erasure

Project description:In this study, we evalauted the transcriptionl profiles of human primordial germ cell-like cell (hPGCLCs) cultured for an extended period on STO feeders in FR10 media for an additional 10 days (D4C10). The hPGCLCs were obtained from two different human embryonic stem cell line (hESCs), UCLA 1 (XX) and UCLA2 (XY) for the RNA sequencing data. For whole genome bisulfite sequencing, we evaluate primed UCLA2 hESCs, directly out of the aggragate hPGCLCs (Day 4= D4) and extended culture hPGCLCs D4C10. Our D4C10 hPGCLCs were compared to prior RNA-sequencing data generated in our laboraty, which revealed that D4C10 hPGCLCs retain germline identy and closely resemble D4 hPGCLCs at the transcriptional level. Our WGBS data revealed that extended culture hPGCLCs at D4C10 have a decrease in CG methlyation, as compared to the starting hESCs and D4 hPGCLCs.

2020-01-31 | GSE139115 | GEO

Project description:RNA-binding proteins DND1 and NANOS3 coordinately suppress SOX4 in processing bodies for restricting the entry of germ cell lineage

| PRJNA1112576 | ENA

Heading towards a dead end: the role of DND1 in germ line differentiation of human iPSCs

Project description:We knocked out DND1 in human iPSCs and analysed its role in pluripotency and differentiation. We showed that general pluripotency gene expression is not affected, but KO iPSCs differentiate less efficiently towards PGC-like cells and remaining PGCLCs show reduced expression of NANOS3 and PRDM1.

2021-10-20 | GSE174464 | GEO

SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

2014-12-26 | GSE60138 | GEO

IGF2BP1 stabilizes OTX2 mRNA in an m6A-dependent manner to restrict human germ cell fate by repressing TFAP2C

Project description:N6-methyladenosine (m6A) is the most abundant and reversible modification on messenger RNAs. The differential m6A profiles in different cell types are installed by writers (such as METTL3) and removed by erasers (such as FTO). The m6A-modified RNAs are recognized by readers to trigger downstream regulation of RNA metabolism, eventually contributing to the regulation of cell fates. Primordial germ cells (PGCs) are specified early during embryogenesis and establish the germ cell lineage for transmitting genetic and epigenetic information from parents to offspring. Defects in the establishment of germline may lead to infertility, germ cell tumors, and birth defects. Despite extensive research, the m6A-mediated epigenetic regulation of the specification of PGCs remains elusive. In this study, we discovered that knock-out of m6A writer or over-expression of erasers leads to increased percentage of human PGC-like cells (hPGCLCs) induced from embryonic stem cells. We identified the m6A reader IGF2BP1 as the key factor for restricting hPGCLC fate induction by stabilizing OTX2 mRNAs in an m6A-dependent manner. Moreover, we discovered that OTX2 suppresses TFAP2C during germ cell lineage specification. In summary, we characterized the m6A-IGF2BP1-OTX2-TFAP2C axis in restricting the specification of human germ cell fate.

2024-04-30 | PXD051996 |

The histone demethylase KDM2B regulates human primordial germ cell-like cells specification

Project description:Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study in vivo as it occurs immediately after blastocyst implantation. The establishment of in vitro human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase KDM2B in male fetal germ cells (FGCs) but not in male somatic cells. Besides, KDM2B shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of KDM2B in germ cell development. Although deletion of KDM2B had no significant effects on human embryonic stem cell (hESC)’s pluripotency, loss of KDM2B dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to KDM2B’s loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, KDM2B suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.

2021-01-10 | GSE160287 | GEO

A critical but divergent role of PRDM14 in human primordial germ cell fate revealed by inducible degrons [ChIP-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 | GSE138674 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data