A tripartite transcription factor network regulates primordial germ cell specification in mice
Erna Magnúsdóttir,Erna Magnúsdóttir,Erna Magnúsdóttir,Sabine Dietmann,Kazuhiro Murakami,Kazuhiro Murakami,Ufuk Günesdogan,Ufuk Günesdogan,Fuchou Tang,Fuchou Tang,Fuchou Tang,Siqin Bao,Siqin Bao,Siqin Bao,Evangelia Diamanti,Kaiqin Lao,Berthold Göttgens,M. Azim Surani,M. Azim Surani +18 more
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TLDR
It is shown that BLIMP1 binds directly to repress somatic and cell proliferation genes and directly induces AP2γ, which together with PRDM14 initiates the PGC-specific fate, and the unprecedented resetting of the epigenome towards a basal state.Abstract:
Surani and colleagues use single-cell transcriptomics analysis in a model of mouse primordial germ cell specification to analyse the collaboration between three transcription factors, BLIMP1, PRDM14 and AP2γ, in determining germ cell fate. They find that BLIMP1 binds directly to repress somatic and cell proliferation genes, and at the same time induces AP2γ, which acts together with PRDM14. The three factors are sufficient for specification and form a tripartite interdependent transcriptional network.read more
Citations
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SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate
Naoko Irie,Naoko Irie,Leehee Weinberger,Walfred W. C. Tang,Walfred W. C. Tang,Toshihiro Kobayashi,Toshihiro Kobayashi,Sergey Viukov,Yair S. Manor,Sabine Dietmann,Jacob H. Hanna,M. Azim Surani,M. Azim Surani +12 more
TL;DR: It is demonstrated that specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline.
Journal ArticleDOI
A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development
Walfred W. C. Tang,Walfred W. C. Tang,Sabine Dietmann,Naoko Irie,Naoko Irie,Harry G. Leitch,Vasileios I. Floros,Charles R. Bradshaw,Jamie A. Hackett,Jamie A. Hackett,Patrick F. Chinnery,M. Azim Surani,M. Azim Surani +12 more
TL;DR: It is shown that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4, which drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation.
Journal ArticleDOI
The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells
Fan Guo,Liying Yan,Liying Yan,Hongshan Guo,Lin Li,Boqiang Hu,Yangyu Zhao,Yangyu Zhao,Jun Yong,Yuqiong Hu,Xiaoye Wang,Xiaoye Wang,Yuan Wei,Yuan Wei,Wei Wang,Wei Wang,Rong Li,Rong Li,Jie Yan,Jie Yan,Xu Zhi,Xu Zhi,Yan Zhang,Yan Zhang,Hongyan Jin,Hongyan Jin,Wenxin Zhang,Wenxin Zhang,Yu Hou,Ping Zhu,Jingyun Li,Ling Zhang,Sirui Liu,Yixin Ren,Yixin Ren,Xiaohui Zhu,Xiaohui Zhu,Lu Wen,Lu Wen,Yi Qin Gao,Fuchou Tang,Jie Qiao +41 more
TL;DR: The transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage is analyzed at single-cell and single-base resolutions and paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.
Journal ArticleDOI
Formative pluripotency: the executive phase in a developmental continuum.
TL;DR: A third phase of pluripotency is proposed to exist as part of a developmental continuum between the naïve and primed phases, entailing remodelling of transcriptional, epigenetic, signalling and metabolic networks to constitute multi-lineage competence and responsiveness to specification cues.
Journal ArticleDOI
Specification and epigenetic programming of the human germ line.
Walfred W. C. Tang,Toshihiro Kobayashi,Naoko Irie,Sabine Dietmann,Sabine Dietmann,M. Azim Surani +5 more
TL;DR: The overall developmental dynamics of human and mouse germline cells appear to be similar, but there are crucial mechanistic differences in PGC specification, reflecting divergence in the regulation of pluripotency and early development.
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