FEBS Open Bio (Jul 2024)

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

  • Cong Wan,
  • Yaping Huang,
  • Xingguo Xue,
  • Gang Chang,
  • Mei Wang,
  • Xiao‐Yang Zhao,
  • Fang Luo,
  • Zhi‐Zhong Tang

DOI
https://doi.org/10.1002/2211-5463.13810
Journal volume & issue
Vol. 14, no. 7
pp. 1087 – 1100

Abstract

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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.

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