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.

PRDM14 is a critical transcription factor for mouse primordial germ cell specification, but its role in human remains unclear. Here, PRDM14 protein depletion using auxin-inducible degron uncovers a critical role for human germ cell specification, but regulation of a different set of target genes than in mouse.

Details

Title
A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons
Author
Sybirna Anastasiya 1 ; Tang Walfred W C 2 ; Pierson Smela Merrick 2   VIAFID ORCID Logo  ; Dietmann Sabine 3 ; Gruhn, Wolfram H 2 ; Brosh Ran 4   VIAFID ORCID Logo  ; Azim, Surani M 5   VIAFID ORCID Logo 

1  Henry Wellcome Building of Cancer and Developmental Biology, Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, UK; University of Cambridge, Physiology, Development and Neuroscience Department, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
2  Henry Wellcome Building of Cancer and Developmental Biology, Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, UK (GRID:grid.5335.0); University of Cambridge, Physiology, Development and Neuroscience Department, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
3  University of Cambridge, Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
4  NYU Langone Health, Institute for Systems Genetics, New York, USA (GRID:grid.137628.9) (ISNI:0000 0004 1936 8753) 
5  Henry Wellcome Building of Cancer and Developmental Biology, Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, UK (GRID:grid.137628.9); University of Cambridge, Physiology, Development and Neuroscience Department, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-15042-0
ProQuest document ID
2375481170
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.