1. Direct reprogramming of human Sertoli cells into male germline stem cells with the self-renewal and differentiation potentials via overexpressing DAZL/DAZ2/BOULE genes
- Author
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Qianqian Qiu, Qingqing Yuan, Liping Wen, Zheng Li, Min Sun, Wei Chen, Wenhui Zhang, Fan Zhou, Yinghong Cui, and Zuping He
- Subjects
Male ,Proteomics ,endocrine system ,Somatic cell ,Transplantation, Heterologous ,Mice, Nude ,Haploidy ,Biology ,Biochemistry ,Article ,Germline ,DAZL ,male germline stem cells ,Genetics ,medicine ,Animals ,Humans ,Cell Self Renewal ,Cells, Cultured ,DAZL/DAZ2/BOULE genes ,Sertoli Cells ,Boule ,Gene Expression Profiling ,reprogramming ,RNA-Binding Proteins ,human Sertoli cells ,Cell Differentiation ,Cell Biology ,self-renewal and differentiation ,Cellular Reprogramming ,Sertoli cell ,Spermatids ,Spermatogonia ,Cell biology ,medicine.anatomical_structure ,Ploidy ,Stem cell ,Reprogramming ,Stem Cell Transplantation ,Developmental Biology - Abstract
Summary We propose a new concept that human somatic cells can be converted to become male germline stem cells by the defined factors. Here, we demonstrated that the overexpression of DAZL, DAZ2, and BOULE could directly reprogram human Sertoli cells into cells with the characteristics of human spermatogonial stem cells (SSCs), as shown 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 spermatocytes and haploid spermatids in vitro. Human Sertoli cell-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 and 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., Highlights • Human Sertoli cells can be converted into SSCs by overexpressing DAZ family genes • Human Sertoli cell-derived cells have phenotypic features with SSCs in vivo • Human Sertoli cell-derived SSCs differentiate into haploid spermatids in vitro • Human Sertoli cell-derived SSCs have normal chromosomes and no gene microdeletion, In this article, Zuping He and colleagues show that human Sertoli cells can be converted directly into human spermatogonial stem cells that are able to self-renew in vivo and differentiate into spermatocytes and haploid spermatids in vitro via the overexpression of three DAZ family genes.
- Published
- 2021