Capturing human trophoblast development with naive pluripotent stem cells in vitro

Shingo Io¹, Mio Kabata², Yoshiki Iemura², Katsunori Semi², Nobuhiro Morone³, Atsutaka Minagawa⁴, Bo Wang⁴, Ikuhiro Okamoto⁵, Tomonori Nakamura⁶, Yoji Kojima⁷, Chizuru Iwatani⁸, Hideaki Tsuchiya⁸, Belinda Kaswandy², Eiji Kondoh⁹, Shin Kaneko⁴, Knut Woltjen², Mitinori Saitou⁷, Takuya Yamamoto¹⁰, Masaki Mandai⁹, Yasuhiro Takashima¹¹

Affiliations

¹ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
² Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan.
³ MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK.
⁴ Department of Cell Growth and Differentiation, CiRA, Kyoto University, Kyoto 606-8507, Japan.
⁵ Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan.
⁶ Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; The HAKUBI Center for Advanced Research, Kyoto University, Kyoto 606-8501, Japan.
⁷ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan.
⁸ Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 520-2192, Japan.
⁹ Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
¹⁰ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; AMED-CREST, AMED, Tokyo 100-0004, Japan; Medical Risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Projects (AIP), Kyoto 606-8507, Japan.
¹¹ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan. Electronic address: y.takashima@cira.kyoto-u.ac.jp.

PMID: 33831365
DOI: 10.1016/j.stem.2021.03.013

Capturing human trophoblast development with naive pluripotent stem cells in vitro

Shingo Io et al. Cell Stem Cell. 2021.

. 2021 Jun 3;28(6):1023-1039.e13.

doi: 10.1016/j.stem.2021.03.013. Epub 2021 Apr 7.

Authors

Affiliations

¹ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
² Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan.
³ MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK.
⁴ Department of Cell Growth and Differentiation, CiRA, Kyoto University, Kyoto 606-8507, Japan.
⁵ Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan.
⁶ Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; The HAKUBI Center for Advanced Research, Kyoto University, Kyoto 606-8501, Japan.
⁷ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan.
⁸ Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 520-2192, Japan.
⁹ Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
¹⁰ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; AMED-CREST, AMED, Tokyo 100-0004, Japan; Medical Risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Projects (AIP), Kyoto 606-8507, Japan.
¹¹ Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan. Electronic address: y.takashima@cira.kyoto-u.ac.jp.

PMID: 33831365
DOI: 10.1016/j.stem.2021.03.013

Abstract

Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placenta-derived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.

Keywords: amnion; cytotrophoblast; early pregnancy; extraembryonic tissue; implantation; naive pluripotent stem cells; placenta; primed pluripotent stem cells; trophectoderm; trophoblast.

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Conflict of interest statement

Declaration of interests S.I. and Y.T. are co-inventors on a patent describing the generation of trophectoderm-like cells from naïve human pluripotent stem cells.

Comment in

The treasure inside human naive pluripotency, generation of trophectoderm and blastoids.
De Santis R, Brivanlou AH. De Santis R, et al. Cell Stem Cell. 2021 Jun 3;28(6):985-987. doi: 10.1016/j.stem.2021.05.010. Cell Stem Cell. 2021. PMID: 34087157

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Capturing human trophoblast development with naive pluripotent stem cells in vitro

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Capturing human trophoblast development with naive pluripotent stem cells in vitro

Authors

Affiliations

Abstract

Conflict of interest statement

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