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27 April 2017 Clonal variation of human induced pluripotent stem cells for induction into the germ cell fate
Shihori Yokobayashi, Keisuke Okita, Masato Nakagawa, Tomonori Nakamura, Yukihiro Yabuta, Takuya Yamamoto, Mitinori Saitou
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Abstract

The mechanisms for human germ cell development have remained largely unknown, due to the difficulty in obtaining suitable experimental materials. The establishment of an in vitro system to reconstitute human germ cell development will thus provide a critical opportunity to understand its mechanisms at a molecular level. It has previously been shown that human induced pluripotent stem cells (hiPSCs) are first induced into incipient mesoderm-like cells (iMeLCs), which are in turn induced into primordial germ-cell like cells (PGCLCs) with gene expression properties similar to early migratory PGCs. Here, we report that the efficiency of PGCLC induction varies among hiPSC clones, and, interestingly, the clonal variations in PGCLC induction efficiency are reflected in the gene expression states of the iMeLCs. Remarkably, the expression levels of EOMES, MIXL1, or T in the iMeLCs are positively correlated with the efficiency of subsequent PGCLC generation, while the expressions of CDH1, SOX3, or FGF2 are negatively correlated. These results indicate that the expression changes of these genes occurring during iMeLC induction are key markers indicative of successful induction of PGCLCs, and furthermore, that hiPSC clones have different properties that influence their responsivity to the iMeLC induction. Our study thus provides important insights into the mechanism of hPGC specification as well as the development of a better strategy for inducing human germ cell fate from PSCs in vitro.

Summary Sentence

Gene expression responses to activin A/WNT signaling vary among clones of human induced pluripotent stem cells, and these differences greatly reflect the clonal variations in the induction efficiency into in vitro primordial germ cells.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com
Shihori Yokobayashi, Keisuke Okita, Masato Nakagawa, Tomonori Nakamura, Yukihiro Yabuta, Takuya Yamamoto, and Mitinori Saitou "Clonal variation of human induced pluripotent stem cells for induction into the germ cell fate," Biology of Reproduction 96(6), 1154-1166, (27 April 2017). https://doi.org/10.1093/biolre/iox038
Received: 19 January 2017; Accepted: 26 April 2017; Published: 27 April 2017
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