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

Anastasiya Sybirna | Walfred W C Tang | Merrick Pierson Smela | Sabine Dietmann | Wolfram H Gruhn | Ran Brosh | M Azim Surani
Nature communications | 2020

PRDM14 is a crucial regulator of mouse primordial germ cells (mPGCs), 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 hPGC-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.

Pubmed ID: 32152282

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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RRID:SCR_002105

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RRID:SCR_002285

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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RRID:SCR_005622

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RRID:SCR_006802

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RRID:SCR_008452

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RRID:SCR_008520

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RRID:SCR_008539

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RRID:SCR_009154

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LIMMA (tool)

RRID:SCR_010943

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RRID:SCR_011847

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RRID:SCR_013575

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RRID:SCR_014583

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RRID:SCR_015687

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RRID:SCR_016366

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RRID:SCR_019547

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ChIPseeker (tool)

RRID:SCR_021322

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RRID:CVCL_0063

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