GATA Transcription Factors, SOX17 and TFAP2C, Drive the Human Germ-cell Specification Program

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2021 Feb 20

PMID 33608411

Citations 29

Authors

Yoji Kojima

Chika Yamashiro

Yusuke Murase

Yukihiro Yabuta

Ikuhiro Okamoto

Chizuru Iwatani

Hideaki Tsuchiya

Masataka Nakaya

Tomoyuki Tsukiyama

Tomonori Nakamura

Takuya Yamamoto

Mitinori Saitou

Affiliations

Soon will be listed here.

Abstract

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, , , and , which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, or , immediate BMP effectors, combined with and , generated hPGCLCs. / knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas / expression remained unaffected in , , or knockouts. In cynomolgus monkeys, a key model for human development, , , and 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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References

Shao Y, Taniguchi K, Gurdziel K, Townshend R, Xue X, Aw Yong K . Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche. Nat Mater. 2016; 16(4):419-425. PMC: 5374007. DOI: 10.1038/nmat4829. View

Ohta H, Kurimoto K, Okamoto I, Nakamura T, Yabuta Y, Miyauchi H . expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate. EMBO J. 2017; 36(13):1888-1907. PMC: 5494472. DOI: 10.15252/embj.201695862. View

Johnson A, Richardson E, Bachvarova R, Crother B . Evolution of the germ line-soma relationship in vertebrate embryos. Reproduction. 2011; 141(3):291-300. DOI: 10.1530/REP-10-0474. View

Kurek D, Neagu A, Tastemel M, Tuysuz N, Lehmann J, van de Werken H . Endogenous WNT signals mediate BMP-induced and spontaneous differentiation of epiblast stem cells and human embryonic stem cells. Stem Cell Reports. 2014; 4(1):114-128. PMC: 4297870. DOI: 10.1016/j.stemcr.2014.11.007. View

Pierson Smela M, Sybirna A, Wong F, Surani M . Testing the role of SOX15 in human primordial germ cell fate. Wellcome Open Res. 2019; 4:122. PMC: 6758833. DOI: 10.12688/wellcomeopenres.15381.2. View

Ohinata Y, Payer B, OCarroll D, Ancelin K, Ono Y, Sano M . Blimp1 is a critical determinant of the germ cell lineage in mice. Nature. 2005; 436(7048):207-13. DOI: 10.1038/nature03813. View

Cong L, Ran F, Cox D, Lin S, Barretto R, Habib N . Multiplex genome engineering using CRISPR/Cas systems. Science. 2013; 339(6121):819-23. PMC: 3795411. DOI: 10.1126/science.1231143. View

Sasaki K, Yokobayashi S, Nakamura T, Okamoto I, Yabuta Y, Kurimoto K . Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells. Cell Stem Cell. 2015; 17(2):178-94. DOI: 10.1016/j.stem.2015.06.014. View

Drukker M, Tang C, Ardehali R, Rinkevich Y, Seita J, Lee A . Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells. Nat Biotechnol. 2012; 30(6):531-42. PMC: 3672406. DOI: 10.1038/nbt.2239. View

10.

Tremblay M, Sanchez-Ferras O, Bouchard M . GATA transcription factors in development and disease. Development. 2018; 145(20). DOI: 10.1242/dev.164384. View

11.

Kanai-Azuma M, Kanai Y, Gad J, Tajima Y, Taya C, Kurohmaru M . Depletion of definitive gut endoderm in Sox17-null mutant mice. Development. 2002; 129(10):2367-79. DOI: 10.1242/dev.129.10.2367. View

12.

Yamaji M, Seki Y, Kurimoto K, Yabuta Y, Yuasa M, Shigeta M . Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet. 2008; 40(8):1016-22. DOI: 10.1038/ng.186. View

13.

Guo F, Yan L, Guo H, Li L, Hu B, Zhao Y . The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells. Cell. 2015; 161(6):1437-52. DOI: 10.1016/j.cell.2015.05.015. View

14.

Krendl C, Shaposhnikov D, Rishko V, Ori C, Ziegenhain C, Sass S . GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency. Proc Natl Acad Sci U S A. 2017; 114(45):E9579-E9588. PMC: 5692555. DOI: 10.1073/pnas.1708341114. View

15.

Extavour C, Akam M . Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development. 2003; 130(24):5869-84. DOI: 10.1242/dev.00804. View

16.

Kong S, Li G, Loh S, Sung W, Liu E . Cellular reprogramming by the conjoint action of ERα, FOXA1, and GATA3 to a ligand-inducible growth state. Mol Syst Biol. 2011; 7:526. PMC: 3202798. DOI: 10.1038/msb.2011.59. View

17.

Luckett W . The development of primordial and definitive amniotic cavities in early Rhesus monkey and human embryos. Am J Anat. 1975; 144(2):149-67. DOI: 10.1002/aja.1001440204. View

18.

Nakamura T, Okamoto I, Sasaki K, Yabuta Y, Iwatani C, Tsuchiya H . A developmental coordinate of pluripotency among mice, monkeys and humans. Nature. 2016; 537(7618):57-62. DOI: 10.1038/nature19096. View

19.

Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K . A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. Sci Rep. 2014; 4:3594. PMC: 3884228. DOI: 10.1038/srep03594. View

20.

Irie N, Weinberger L, Tang W, Kobayashi T, Viukov S, Manor Y . SOX17 is a critical specifier of human primordial germ cell fate. Cell. 2014; 160(1-2):253-68. PMC: 4310934. DOI: 10.1016/j.cell.2014.12.013. View