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The RNA-Binding Protein DND1 Acts Sequentially as a Negative Regulator of Pluripotency and a Positive Regulator of Epigenetic Modifiers Required for Germ Cell Reprogramming

ABSTRACT: Analysis of our transcriptome and RNA immunoprecipitation experiments indicate DND1 acts as a positive regulator of chromatin modifiers in male germ cells, linking RNA binding proteins and epigenetic regulation.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE132719 | GEO | 2019/06/14

REPOSITORIES: GEO

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The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.

Project description: Not available

| S-EPMC6803376 | biostudies-literature

The RNA-Binding Protein DND1 Acts Sequentially as a Negative Regulator of Pluripotency and a Positive Regulator of Epigenetic Modifiers Required for Germ Cell Reprogramming

Project description:The RNA-Binding Protein DND1 Acts Sequentially as a Negative Regulator of Pluripotency and a Positive Regulator of Epigenetic Modifiers Required for Germ Cell Reprogramming

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Gene expression analysis of control and Dnd1-cKO germ cells at E11.5.

Project description:The present investigation was to identify transcriptomic changes of control and Dnd1-cKO PGCs at E11.5 by RNA-seq analysis. We identified 181 upregulated and 141 downregulated genes in Dnd1-cKO PGCs.

2022-12-28 | GSE218770 | GEO

Arabidopsis dnd1

Project description:Transcript profiling of dnd1 mutant grown in control condition.

2013-01-17 | E-MEXP-3768 | biostudies-arrayexpress

Gene expression analysis of control and Dnd1-cKO germ cells at E12.5 and E13.5.

Project description:The present investigation was to identify transcriptomic changes of control and Dnd1-cKO PGCs at E12.5 and E13.5 by microarray comparison. We identified 1470 upregulated and 924 downregulated genes in Dnd1-cKO PGCs.

2022-12-28 | GSE218744 | GEO

The RNA Binding Protein Dead End1 Is Differentially Expressed in Male Germ Cells During Late Gestation and Targets Chromatin Modifiers and Translational Machinery

Project description:DND1 is essential to maintain germ cell identity. Loss of Dnd1 function results in trans-differentiation of germ cells to somatic fates in zebrafish or the formation of teratomas in mice. To explore the mechanistic role of DND1, we recently developed a transgenic mouse line in which a functional fusion protein between DND1 and GFP is expressed from the endogenous locus (Dnd1GFP). Surprisingly, we found that this reporter distinguishes two male germ cell populations (MGCs) during late gestation cell cycle arrest (G0). Most MGCs express low levels of DND1-GFP, but 5-12% of the population express high levels of DND1-GFP. An RNA-seq time course during late gestation revealed that Dnd1 transcript levels as well as transcript levels for multiple epigenetic regulators are 5-10-fold higher in DND1-GFP-hi cells. Furthermore, using antibodies against DND1-GFP for RNA immunoprecipitation (RIP) time course sequencing during late gestation, we identified multiple epigenetic and translational regulators that are binding targets of DND1 during G0. Among these targets are DNA methyltransferases (Dnmts), the enzyme Setdb1 that imposes the nuclear lamina associated repressive histone mark (H3K9me3), five Tudor domain proteins (Tdrds), four actin dependent regulators (Smarcs), and a group of ribosomal and Golgi proteins. These data suggest that DND1 binds to transcripts of a group of epigenetic enzymes and gates their translation during MGC G0 arrest in late gestation.

2022-10-18 | GSE197610 | GEO

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.

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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

Transcriptome of nascent teratoma cell-derived pluripotent stem cells, Dnd1-KD ESCs and control ESCs.

Project description:We report transcriptome of nascent teratoma cell-derived pluripotent stem cells, Dnd1-KD ESCs and control ESC by RNA-seq.

2018-08-16 | GSE118582 | GEO

HEK293T LC-MSMS of DND1 immunoprecipitations

Project description:HEK293T interactomes of transiently expressed RNA-binding protein DND1: WT (replicates P9-1, P10-1, P18-1), R98A RNA binding mutant (replicates P9-2, P10-2, P18-2) and 1-235 dsRBD truncation mutant (replicates P9-3, P10-3, P18-3)

2022-05-30 | PXD024666 | Pride

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