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

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Listed:
  • Anastasiya Sybirna

    (Henry Wellcome Building of Cancer and Developmental Biology
    University of Cambridge
    University of Cambridge)

  • Walfred W. C. Tang

    (Henry Wellcome Building of Cancer and Developmental Biology
    University of Cambridge)

  • Merrick Pierson Smela

    (Henry Wellcome Building of Cancer and Developmental Biology
    University of Cambridge)

  • Sabine Dietmann

    (University of Cambridge)

  • Wolfram H. Gruhn

    (Henry Wellcome Building of Cancer and Developmental Biology
    University of Cambridge)

  • Ran Brosh

    (NYU Langone Health)

  • M. Azim Surani

    (Henry Wellcome Building of Cancer and Developmental Biology
    University of Cambridge
    University of Cambridge)

Abstract

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.

Suggested Citation

  • Anastasiya Sybirna & Walfred W. C. Tang & Merrick Pierson Smela & Sabine Dietmann & Wolfram H. Gruhn & Ran Brosh & M. Azim Surani, 2020. "A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15042-0
    DOI: 10.1038/s41467-020-15042-0
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    Cited by:

    1. Sivakamasundari Vijayakumar & Roberta Sala & Gugene Kang & Angela Chen & Michelle Ann Pablo & Abidemi Ismail Adebayo & Andrea Cipriano & Jonas L. Fowler & Danielle L. Gomes & Lay Teng Ang & Kyle M. Lo, 2023. "Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Quentin I. B. Lemaître & Natascha Bartsch & Ian U. Kouzel & Henriette Busengdal & Gemma Sian Richards & Patrick R. H. Steinmetz & Fabian Rentzsch, 2023. "NvPrdm14d-expressing neural progenitor cells contribute to non-ectodermal neurogenesis in Nematostella vectensis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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