Derivation of functional trophoblast stem cells from primed human pluripotent stem cells

Francesca Soncin; Robert Morey; Tony Bui; Daniela F Requena; Virginia Chu Cheung; Sampada Kallol; Ryan Kittle; Madeline G Jackson; Omar Farah; Jennifer Chousal; Morgan Meads; Donald Pizzo; Mariko Horii; Kathleen M Fisch; Mana M Parast

doi:10.1016/j.stemcr.2022.04.013

Derivation of functional trophoblast stem cells from primed human pluripotent stem cells

Stem Cell Reports. 2022 Jun 14;17(6):1303-1317. doi: 10.1016/j.stemcr.2022.04.013. Epub 2022 May 19.

Authors

Affiliations

¹ Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA.
² Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, USA.
³ Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
⁵ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, USA.
⁶ Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: mparast@ucsd.edu.

Abstract

Trophoblast stem cells (TSCs) have recently been derived from human embryos and early-first-trimester placenta; however, aside from ethical challenges, the unknown disease potential of these cells limits their scientific utility. We have previously established a bone morphogetic protein 4 (BMP4)-based two-step protocol for differentiation of primed human pluripotent stem cells (hPSCs) into functional trophoblasts; however, those trophoblasts could not be maintained in a self-renewing TSC-like state. Here, we use the first step from this protocol, followed by a switch to newly developed TSC medium, to derive bona fide TSCs. We show that these cells resemble placenta- and naive hPSC-derived TSCs, based on their transcriptome as well as their in vitro and in vivo differentiation potential. We conclude that primed hPSCs can be used to generate functional TSCs through a simple protocol, which can be applied to a widely available set of existing hPSCs, including induced pluripotent stem cells, derived from patients with known birth outcomes.

Keywords: cytotrophoblast; naive pluripotent stem cells; placenta; primed pluripotent stem cells; trophoblast stem cells.

Publication types

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

MeSH terms

Cell Differentiation
Female
Humans
Induced Pluripotent Stem Cells*
Placenta
Pluripotent Stem Cells*
Pregnancy
Trophoblasts

Abstract

Publication types

MeSH terms

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