TY - JOUR
T1 - Germline competency of human embryonic stem cells depends on eomesodermin
AU - Chen, Di
AU - Liu, Wanlu
AU - Lukianchikov, Anastasia
AU - Hancock, Grace V.
AU - Zimmerman, Jill
AU - Lowe, Matthew G.
AU - Kim, Rachel
AU - Galic, Zoran
AU - Irie, Naoko
AU - Surani, M. Azim
AU - Jacobsen, Steven E.
AU - Clark, Amander T.
N1 - Funding Information:
1Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, California, USA; 2Molecular Biology Institute, University of California, Los Angeles, California, USA; 3Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California, USA; 4Department of Medicine, University of California, Los Angeles, California, USA; 5Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK; 6Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK; 7Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK; 8Department of Biological Chemistry, University of California, Los Angeles, California, USA; 9Howard Hughes Medical Institute, University of California, Los Angeles, California, USA and 10Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA ∗Correspondence: Department of Molecular Cell and Developmental Biology, 615 Charles E Young Drive South, University of California Los Angeles, Los Angeles, CA 90095, USA. E-mail: clarka@ucla.edu †Grant Support: All experiments, with the exception of human hESC derivation, were funded by R01 HD079546 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) (ATC) and supported by Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research NIH-NCATS UCLA CTSI Grant Number UL1TR0001881. No NIH funds were used for human embryo culture or hESC derivation. Instead, the derivation of hESC lines was funded by the California Institute for Regenerative Medicine, the UCLA Eli, and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (BSCRC). Di Chen is supported by a training grant from the UCLA BSCRC. Wanlu Liu is supported by Philip J. Whitcome fellowship from the UCLA Molecular Biology Institute and a scholarship from the Chinese Scholarship Council. Human fetal tissue was obtained from the Laboratory of Developmental Biology, University of Washington, Seattle, which is supported by NIH Award Number 5R24HD000836 from the NICHD.
Publisher Copyright:
©The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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 TGFß 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.
AB - 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 TGFß 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.
KW - EOMES
KW - Embryonic stem cells
KW - Human
KW - Primordial germ cells
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U2 - 10.1093/biolre/iox138
DO - 10.1093/biolre/iox138
M3 - Article
C2 - 29091993
AN - SCOPUS:85040132514
SN - 0006-3363
VL - 97
SP - 850
EP - 861
JO - Biology of Reproduction
JF - Biology of Reproduction
IS - 6
ER -
