Development and application of haploid embryonic stem cells

• Haploid embryonic stem cells (haESCs) combine the advantages of haploidy and pluripotency, enabling efficient genetic screening and drug-targeted therapy. • The establishment of haESCs in various species, from medaka fish to mammals, has overcome the challenge of haploid cell culture and opened new avenues for genetic research. • HaESCs serve as powerful tools for studying X chromosome inactivation, haploid diploidization, and gamete substitution, with potential applications in reproductive medicine. • The review highlights the historical milestones and future directions in haESC research, emphasizing their significance in life sciences and clinical translation.