Placenta-derived macaque trophoblast stem cells: differentiation to syncytiotrophoblasts and extravillous trophoblasts reveals phenotypic reprogramming

Jenna Kropp Schmidt*, Logan T. Keding, Lindsey N. Block, Gregory J. Wiepz, Michelle R. Koenig, Michael G. Meyer, Brittany M. Dusek, Kamryn M. Kroner, Mario J. Bertogliat, Avery R. Kallio, Katherine D. Mean, Thaddeus G. Golos

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Nonhuman primates are excellent models for studying human placentation as experimental manipulations in vitro can be translated to in vivo pregnancy. Our objective was to develop macaque trophoblast stem cells (TSCs) as an in vitro platform for future assessment of primate trophoblast development and function. Macaque TSC lines were generated by isolating first and second trimester placental villous cytotrophoblasts followed by culture in TSC medium to maintain cellular proliferation. TSCs grew as mononuclear colonies, whereas upon induction of syncytiotrophoblast (ST) differentiation multinuclear structures appeared, indicative of syncytium formation. Chorionic gonadotropin secretion was > 4000-fold higher in ST culture media compared to TSC media. The secretion of chorionic gonadotropin by TSC-derived ST reflects a reprogramming of macaque TSCs to an earlier pregnancy phenotype. Characteristic trophoblast hallmarks were defined in TSCs and ST including expression of C19MC miRNAs and the macaque placental nonclassical MHC class I molecule, Mamu-AG. Extravillous trophoblasts (EVTs) were derived that express macaque EVT markers Mamu-AG and CD56, and also secrete high levels of MMP2. Our analyses of macaque TSCs suggests that these cells represent a proliferative, self-renewing population capable of differentiating to STs and EVTs in vitro thereby establishing an experimental model of primate placentation.

Original languageEnglish (US)
Article number19159
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

Funding

The authors would like to thank the Wisconsin National Primate Research Center units including the Scientific Protocol Implementation, Veterinary Services, Colony Management and Pathology Services Units, especially Dr. Kevin Brunner and Michele Schotzko, for assisting in collection of macaque placentas. The authors also extend thanks to the University of Wisconsin-Madison Biotechnology Center Gene Expression Center and DNA Sequencing Facility for providing single cell library preparation and next generation sequencing services. We would also like to thank the University of Wisconsin-Madison Biotechnology Center Bioinformatics Resource Center, particularly Drs. Derek Pavelec and Mark Berres, for analysis of RNA-sequencing datasets. The authors would also like to acknowledge funding support by the following funding sources: P51 OD011106-54 to the Wisconsin National Primate Research Center; R01 AI132419-01A1, R01 AI107157-01A1, and R21 AI136012-01 to TGG; T32GM081061 and F31HD100057 to LNB; and K99 HD099154-01 to JKS. We also acknowledge support for the BD LSRFortessa flow cytometry instrument by the University of Wisconsin Carbone Cancer Center Support (NIH grant P30 CA014520).

ASJC Scopus subject areas

  • General

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