title: Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells.
abstract: The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs) impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development.
authors: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan ; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors: I-Ying
authors: IY
authors: Lin
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors: Feng-Lan
authors: FL
authors: Chiu
authors: Institute of Statistical Science, Academia Sinica, Taipei 115, Taiwan.
authors: Chen-Hsiang
authors: CH
authors: Yeang
authors: Graduate Institute of Clinical Genomics, College of Medicine, National Taiwan University, Taipei 106, Taiwan ; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, National Taiwan University Hospital, Taipei 100, Taiwan.
authors: Hsin-Fu
authors: HF
authors: Chen
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors: Ching-Yu
authors: CY
authors: Chuang
authors: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors: Shii-Yi
authors: SY
authors: Yang
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors: Pei-Shan
authors: PS
authors: Hou
authors: Institute of Statistical Science, Academia Sinica, Taipei 115, Taiwan.
authors: Nardnisa
authors: N
authors: Sintupisut
authors: Graduate Institute of Clinical Genomics, College of Medicine, National Taiwan University, Taipei 106, Taiwan ; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, National Taiwan University Hospital, Taipei 100, Taiwan.
authors: Hong-Nerng
authors: HN
authors: Ho
authors: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan ; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors: Hung-Chih
authors: HC
authors: Kuo
authors: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan ; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors: Kuo-I
authors: KI
authors: Lin
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D006066:Gonads / Q000196:embryology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D055415:Bone Morphogenetic Protein 4; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D060509:Wnt3A Protein; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1