Germline competency of human embryonic stem cells depends on eomesodermin

Di Chen; Wanlu Liu; Anastasia Lukianchikov; Grace V Hancock; Jill Zimmerman; Matthew G Lowe; Rachel Kim; Zoran Galic; Naoko Irie; M Azim Surani; Steven E Jacobsen; Amander T Clark

doi:10.1093/biolre/iox138

Germline competency of human embryonic stem cells depends on eomesodermin

Biol Reprod. 2017 Jan 1;97(6):850-861. doi: 10.1093/biolre/iox138.

Authors

Di Chen¹, Wanlu Liu², Anastasia Lukianchikov¹, Grace V Hancock^{1

2}, Jill Zimmerman¹, Matthew G Lowe^{1

2}, Rachel Kim³, Zoran Galic^{3

4}, Naoko Irie^{5

6

7}, M Azim Surani^{5

6

7}, Steven E Jacobsen^{1

2

3

8

9}, Amander T Clark^{1

2

3

10}

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, California, USA.
² Molecular Biology Institute, University of California, Los Angeles, California, USA.
³ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California, USA.
⁴ Department of Medicine, University of California, Los Angeles, California, USA.
⁵ Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
⁶ Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
⁷ Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
⁸ Department of Biological Chemistry, University of California, Los Angeles, California, USA.
⁹ Howard Hughes Medical Institute, University of California, Los Angeles, California, USA.
¹⁰ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.

Abstract

In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFβ and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES.

Keywords: EOMES; embryonic stem cells; human; primordial germ cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CRISPR-Cas Systems
Cell Differentiation*
Cell Line
Female
Gene Expression Regulation, Developmental
Germ Cells / cytology*
Human Embryonic Stem Cells / cytology*
Humans
Male
Sequence Analysis, RNA
Signal Transduction*
T-Box Domain Proteins / physiology

Substances

EOMES protein, human
T-Box Domain Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding