PMID- 29398481 OWN - NLM STAT- MEDLINE DCOM- 20190117 LR - 20210109 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 10 IP - 2 DP - 2018 Feb 13 TI - In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells. PG - 509-523 LID - S2213-6711(18)30027-4 [pii] LID - 10.1016/j.stemcr.2018.01.001 [doi] AB - Due to differences across species, the mechanisms of cell fate decisions determined in mice cannot be readily extrapolated to humans. In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs) into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs). These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRalpha1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Taken together, we established a powerful experimental platform to investigate human germ cell development and pathology related to male infertility. CI - Copyright (c) 2018 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Zhao, Yuncheng AU - Zhao Y AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Ye, Shicheng AU - Ye S AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Liang, Dongli AU - Liang D AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Wang, Pengxiang AU - Wang P AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Fu, Jing AU - Fu J AD - Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China. FAU - Ma, Qing AU - Ma Q AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Kong, Ruijiao AU - Kong R AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Shi, Linghong AU - Shi L AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Gong, Xueping AU - Gong X AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Chen, Wei AU - Chen W AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Ding, Wubin AU - Ding W AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. FAU - Yang, Wenjing AU - Yang W AD - Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Zhu, Zijue AU - Zhu Z AD - Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China. FAU - Chen, Huixing AU - Chen H AD - Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China. FAU - Sun, Xiaoxi AU - Sun X AD - Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China. FAU - Zhu, Jun AU - Zhu J AD - Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Li, Zheng AU - Li Z AD - Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China. FAU - Wang, Yuan AU - Wang Y AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Department of Animal Science, Michigan State University, Lansing, MI 48824, USA. Electronic address: ywang@bio.ecnu.edu.cn. LA - eng GR - R01 AA020404/AA/NIAAA NIH HHS/United States GR - ZIC HL006058/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20180201 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (DAZL protein, human) RN - 0 (DMRT1 protein) RN - 0 (Gfra1 protein, mouse) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors) RN - 0 (NANOS3 protein, human) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Azoospermia/*genetics/pathology MH - Cell Culture Techniques MH - Cell Differentiation/genetics MH - Feeder Cells/cytology MH - Gene Expression Regulation, Developmental/genetics MH - Germ Cells/cytology/growth & development MH - Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics MH - Humans MH - Induced Pluripotent Stem Cells/*cytology/pathology MH - Infertility, Male/*genetics/pathology MH - Male MH - Meiosis/genetics MH - Mice MH - Mouse Embryonic Stem Cells/cytology MH - RNA-Binding Proteins/genetics MH - Species Specificity MH - Spermatogonia/cytology/*growth & development/pathology MH - Transcription Factors/genetics PMC - PMC5830957 OTO - NOTNLM OT - infertility OT - non-obstructive azoospermia OT - pluripotent stem cells OT - spermatogonia EDAT- 2018/02/06 06:00 MHDA- 2019/01/18 06:00 PMCR- 2018/02/01 CRDT- 2018/02/06 06:00 PHST- 2017/04/04 00:00 [received] PHST- 2017/12/28 00:00 [revised] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/02/06 06:00 [pubmed] PHST- 2019/01/18 06:00 [medline] PHST- 2018/02/06 06:00 [entrez] PHST- 2018/02/01 00:00 [pmc-release] AID - S2213-6711(18)30027-4 [pii] AID - 10.1016/j.stemcr.2018.01.001 [doi] PST - ppublish SO - Stem Cell Reports. 2018 Feb 13;10(2):509-523. doi: 10.1016/j.stemcr.2018.01.001. Epub 2018 Feb 1.