# HELQ deficiency impairs the induction of primordial germ cell‐like cells

## TL;DR

HELQ deficiency reduces the formation of primordial germ cell-like cells in both mice and humans, suggesting a role in fertility and germline development.

## Contribution

This study reveals HELQ's role in mouse and human primordial germ cell-like cell induction and its connection to male infertility.

## Key findings

- HELQ deficiency significantly reduces mouse PGCLC induction efficiency.
- p53 inhibitor treatment partially rescues PGCLC formation in HELQ-deficient mouse cells.
- HELQ ablation also impairs human PGCLC induction.

## Abstract

Helicase POLQ‐like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq
−/−) could significantly reduce the efficiency of mouse primordial germ cell‐like cell (PGCLC) induction. In addition, Helq
−/− embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

Helicase POLQ‐like (HELQ) is an essential DNA helicase for maintaining genomic stability, and its mutations have been associated with male infertility. We found that absence of HELQ markedly reduces the induction efficiency of mouse primordial germ cell‐like cells in vitro. This reduction can be partially reversed by treatment with a p53 inhibitor. Furthermore, HELQ is also implicated in the induction of human primordial germ cell‐like cells.