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Cell Death Differ. 2018 Mar;25(4):747-764. doi: 10.1038/s41418-017-0015-1. Epub 2018 Jan 5.

Efficient generation of functional haploid spermatids from human germline stem cells by three-dimensional-induced system.

Author information

1
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
2
Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
3
Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
4
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. zupinghe@sjtu.edu.cn.
5
School of Medicine, Hunan Normal University, 371 Tongzhi Road, Changsha, Hunan, 410013, China. zupinghe@sjtu.edu.cn.
6
Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, 200127, China. zupinghe@sjtu.edu.cn.
7
Shanghai Key Laboratory of Reproductive Medicine, Shanghai, 200025, China. zupinghe@sjtu.edu.cn.

Abstract

Generation of functional spermatids from human spermatogonial stem cells (SSCs) in vitro is of utmost importance for uncovering mechanisms underlying human germ cell development and treating infertility. Here we report a three-dimensional-induced (3D-I) system by which human SSCs were efficiently differentiated into functional haploid spermatids. Human SSCs were isolated and identified phenotypically. Meiotic chromatin spreads and DNA content assays revealed that spermatocytes and haploid cells were effectively generated from human SSCs by 3D-I system. Haploid cells derived from human SSCs harbored normal chromosomes and excluded Y chromosome microdeletions. RNA sequencing and bisulfite sequencing analyses reflected similarities in global gene profiles and DNA methylation in human SSCs-derived spermatids and normal round spermatids. Significantly, haploid spermatids generated from human SSCs via 3D-I system were capable of fertilizing mouse oocytes, which subsequently enabled the development of hybrid embryos. This study thus provides invaluable human male gametes for treating male infertility.

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