Haploid pluripotent stem cells, which are capable of self-renewal and differentiation into other cell types with only one set of chromosomes, have been established in several species from haploid embryos. Compared with diploid embryonic stem cells (ESCs), haploid embryonic stem cells (haESCs) are smaller in size, have a prolonged metaphase, and undergo self-doubling during culture. The monoallelic expression of haESCs provides great convenience for recessive inheritance research. Genetically modified haESCs also provide benefits in replacement of the gamete genomes, which not only facilitates the study of the function of imprinted genes but also potentially removes barriers to same-sex reproduction. In this review, we focus on strategies for obtaining haESCs and their potential applications in genetic screening, genomic imprinting, and unisexual reproduction.
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