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Direct reprogramming of human Sertoli cells into male germline stem cells with the self-renewal and differentiation potentials via overexpressing DAZL/DAZ2/BOULE genes

ABSTRACT: In this study, we have demonstrated, for the first time, that overexpression of three genes of DAZ family members, namely DAZL, DAZ2, and BOULE, could directly reprogram human Sertoli cells to the cells with the biochemical phenotypes, the self-renewal and differentiation capacities of human SSCs. This study thus offers invaluable male gametes for treating the infertility of azoospermia patients. We propose a new concept that human somatic cells can be converted to become male germline stem cells by the defined factors. Here we have demonstrated that the overexpression of DAZL, DAZ2, and BOULE could directly reprogram human Sertoli cells into the cells with the characteristics of human spermatogonial stem cells (SSCs), as evidenced by their similar transcriptomes and proteomics with human SSCs. Significantly, human SSCs derived from human Sertoli cells colonized and proliferated in vivo, and they could differentiate into spermatocyte and haploid spermatids in vitro. Human Sertoli cells-derived SSCs excluded Y chromosome microdeletions and assumed normal chromosomes. Collectively, human somatic cells could be converted directly to human SSCs with the self-renewal & differentiation potentials and high safety. This study is of unusual significance, because it provides an effective approach for reprogramming human somatic cells into male germ cells and offers invaluable male gametes for treating male infertility.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184088 | GEO | 2021/09/30

REPOSITORIES: GEO

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