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

Nature Communications
Anastasiya SybirnaM Azim Surani

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.

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Citations

Aug 2, 2020·Seminars in Cancer Biology·Ammad Ahmad FarooqiMassimo Mallardo
Jan 28, 2021·Seminars in Cell & Developmental Biology·Vallari ShuklaEva R Hoffmann
Jan 28, 2021·World Journal of Surgical Oncology·Xiao-Hong MaoPing Huang
Feb 21, 2021·Life Science Alliance·Yoji KojimaMitinori Saitou
Mar 17, 2021·Development·Grace V HancockAmander T Clark
May 13, 2021·Stem Cell Reports·Ramiro AlberioM Azim Surani
Mar 29, 2021·The FEBS Journal·Federico Di TullioErnesto Guccione
May 1, 2021·Biology of Reproduction·Millissia Ben MaamarMichael K Skinner
May 18, 2021·Asian Journal of Urology·Melanie R MüllerDaniel Nettersheim
Jun 12, 2021·Stem Cell Reviews and Reports·Naira Caroline Godoy PieriAndré Furugen Cesar de Andrade
Jul 3, 2021·International Journal of Molecular Sciences·Massimo De FeliciSusanna Dolci
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Oct 1, 2021·Science·Mitinori Saitou, Katsuhiko Hayashi
Oct 16, 2021·Histochemistry and Cell Biology·V K AbdyyevA V Vasiliev

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Methods Mentioned

BETA
flow
fluorescence-activated cell sorting
flow cytometry
RNA-seq
immunoprecipitation
ChIP-seq
ChIP
transfection
FACS
PCR

Software Mentioned

R limma package
DEseq2
JAZ
GSEA
FastQC
GraphPad Prism
Integrative Genomics Viewer
bedtools merge
multiQC
R

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