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Status |
Public on Feb 16, 2021 |
Title |
GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program [Bisulfite-Seq] |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
The in vitro reconstitution of human germ-cell development provides a robust framework for clarifying key underlying mechanisms. Here, we explored transcription factors (TFs) that engender the germ-cell fate in their pluripotent precursors. Unexpectedly, SOX17, TFAP2C, and BLIMP1, which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, GATA3 or GATA2, immediate BMP effectors, combined with SOX17 and TFAP2C, generated hPGCLCs. GATA3/GATA2 knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas GATA3/GATA2 expression remained unaffected in SOX17, TFAP2C, or BLIMP1 knockouts. In cynomolgus monkeys, a key model for human development, GATA3, SOX17, and TFAP2C were co-expressed exclusively in early PGCs. Crucially, the TF-induced hPGCLCs acquired a hallmark of bona fide hPGCs to undergo epigenetic reprogramming and mature into oogonia/gonocytes in xenogeneic reconstituted ovaries. By uncovering a TF circuitry driving the germ line program, our study provides a paradigm for TF-based human gametogenesis.
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Overall design |
Whole Genome Bisulfite Sequence (WGBS): Overexpression of SOX17, TFAP2C, GATA3, clone_1; day77
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Contributor(s) |
Kojima Y, Yamashiro C, Murase Y, Yabuta Y, Okamoto I, Iwatani C, Tsuchiya H, Nakaya M, Tsukiyama T, Nakamura T, Yamamoto T, Saitou M |
Citation(s) |
33608411 |
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Submission date |
Jul 19, 2020 |
Last update date |
Mar 10, 2021 |
Contact name |
Yukihiro Yabuta |
E-mail(s) |
yabyab@anat2.med.kyoto-u.ac.jp
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Organization name |
Kyoto University, Graduate school of medicine
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Department |
Anatomy and Cell Biology
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Street address |
Yoshida-Konoe-cho, Sakyo-ku
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City |
Kyoto |
State/province |
Kyoto |
ZIP/Postal code |
606-8501 |
Country |
Japan |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (1) |
GSM4677539 |
Overexpression of SOX17, TFAP2C, GATA3, clone_1; day77 |
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This SubSeries is part of SuperSeries: |
GSE154691 |
GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program |
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Relations |
BioProject |
PRJNA647204 |
SRA |
SRP272481 |
Supplementary file |
Size |
Download |
File type/resource |
GSE154690_RAW.tar |
375.5 Mb |
(http)(custom) |
TAR (of BIGWIG, TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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