Surrogate Production of Genome Edits Sperm from a Genetically Distant Species

Spermatogonial stem cells (SSCs) are the only type of stem cells in the adult testis that maintain the activity of self-renewal and has the potential for differentiation. By utilizing the technique of SSCs transplantation (SSCT), it is possible to realize the so-called xenogenic “surrogate reproduction”, thus producing the functional gametes of species B with the gonads of species A.    

SSCT provides a powerful tool for production of gametes derived from endangered species or those with desirable traits. However, generation of genome edited gametes from a different species or production of gametes from a phylogenetically distant species such as from a different subfamily, by SSCT, has not been successful.   

Recently, a research group led by Prof. SUN Yonghua from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences achieved, for the first time, “surrogate reproduction” between two species from a different subfamily and obtained cross-subfamily donor derived genome edited SSCT sperm. This study was published in Science China Life Sciences.   

In previous study, the researchers have already established and optimized the “surrogate reproduction” technology for genome edited gametes in fish and obtained maternal-zygotic mutants of lethal genes essential for early embryogenesis efficiently and speedily (J Genet Genomics2020recommended by Faculty of 1000).    

In order to study whethersurrogate reproduction”could be achieved between different fish species to generate donor-derived genome edited gametes, the researchers utilized two small cyprinid fishes, Chinese rare minnow (gobiocypris rarus, for brief: Gr) and zebrafish (danio rerio), which belong to different subfamilies, as donors and recipients for SSCT.    

Firstly, they optimized the process of surrogate reproduction by combining CRISPR/Cas9 genome editing and SSCT technologies, and successfully obtained genome edited sperm of gobiocypris rarus from zebrafish surrogates, with a relative high efficiency.    

They further delicately described the process of the colonization, proliferation, and differentiation of transplanted SSCs in the recipient gonads, and showed that the reconstructed fertile testis contained Gr spermatids and zebrafish testicular somatic cells.    

Interestingly, the researchers found that although the SSCT sperm could only fertilize the Gr eggs, they somehow resembled the sperm of zebrafish host but not donor Gr in morphology and swimming behavior. By RNA-seq analysis of the SSCT sperm and the Gr sperm, they demonstrated that the existence of zebrafish-derived transcripts in the SSCT sperm might affect the development and morphology of SSCT sperm.   

This study for the first time demonstrates the possibility of xenogenic SSCT between different subfamilies, and surrogate production of genome edited gametes from a different species. Thus, it opens a new avenue for accelerating breeding process of commercial fish or even livestock.