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09.03.20 PRDM14 activity in human primordial germ cells differs from development in mouse

last modified Mar 13, 2020 03:51 PM
Sybirna et al. in the Surani lab reveal the role of PRDM14 in human germ cell differentiation using special method for specific and rapid depletion of protein as cells develop in vitro
09.03.20 PRDM14 activity in human primordial germ cells differs from development in mouse

Fig. 6b (excerpt): Down- and up-regulated genes upon loss of PRDM14.

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

 

Sybirna A et al. (2020) Nature Communications 11, 1282.

DOI: 10.1038/s41467-020-15042-0.

 

Abstract from the paper

PRDM14 is a crucial regulator of mouse primordial germ cells (mPGC), 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 human PGC-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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