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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jul 20, 2015 |
Title |
Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells |
Organisms |
Macaca fascicularis; Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Mechanisms underlying human germ cell development are unclear, partly due to difficulties in studying human embryos and lack of suitable experimental systems. Here, we show that human induced pluripotent stem cells (hiPSCs) differentiate into incipient mesoderm-like cells (iMeLCs), which robustly generate human primordial germ cell-like cells (hPGCLCs) that can be purified using the surface markers EpCAM and INTEGRINα6. The transcriptomes of hPGCLCs and primordial germ cells (PGCs) isolated from non-human primates are similar, and although specification of hPGCLCs and mouse PGCs rely on similar signaling pathways, hPGCLC specification transcriptionally activates germline fate without transiently inducing eminent somatic programs. This includes genes important for naive pluripotency and repression of key epigenetic modifiers, concomitant with epigenetic reprogramming. Accordingly, BLIMP1, which represses somatic programs in mice, activates and stabilizes a germline transcriptional circuit and represses a default neuronal differentiation program. Together, these findings provide a foundation for understanding and reconstituting human germ cell development in vitro.
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Overall design |
RNAseq analysis of human induced pluripotent stem cells (hiPSC), incipient mesoderm-like cells (iMeLC) and primordial germ cell-like cells (BLIMP1-2A-tdTomato (BT)/TFAP2C-2A-ECFP (AG) expressing cells or EpCAM/CD49f (CSM) positive cells) RNAseq analysis of mouse embryonic stem cells (mESC), epiblast-like cells (EpiLC) and primordial germ cell-like cells (PGCLC; Blimp1-mVenus (BV) or BV/stella-eCFP (SC) positive cells) Single cell RNAseq analysis of cynomolgus ESCs and gonadal PGCs
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Contributor(s) |
Sasaki K, Yokobayashi S, Nakamura T, Okamoto I, Yabuta Y, Kurimoto K, Ohta H, Moritoki Y, Iwatani C, Tsuchiya H, Sekiguchi K, Sakuma T, Yamamoto T, Mori T, Woltjen K, Nakagawa M, Yamamoto T, Takahashi K, Yamanaka S, Saitou M, Nakamura S |
Citation(s) |
26189426, 28649393 |
Submission date |
Mar 25, 2015 |
Last update date |
May 15, 2019 |
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 (3) |
GPL15907 |
AB 5500xl Genetic Analyzer (Mus musculus) |
GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
GPL19944 |
AB 5500xl Genetic Analyzer (Macaca fascicularis) |
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Samples (74)
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Relations |
BioProject |
PRJNA279357 |
SRA |
SRP056527 |
Supplementary file |
Size |
Download |
File type/resource |
GSE67259_expression_cynomolgus.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
GSE67259_expression_human.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
GSE67259_expression_mouse.txt.gz |
637.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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