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Published Online: 20 September 2018

Sex-Specific Gene Expression Differences Are Evident in Human Embryonic Stem Cells and During In Vitro Differentiation of Human Placental Progenitor Cells

Publication: Stem Cells and Development
Volume 27, Issue Number 19


The placenta is a short-lived tissue required for embryonic growth and survival, and it is fetal derived. Fetal sex influences gestation, and many sexual dimorphic diseases have origins in utero. There is sex-biased gene expression in third-trimester human placentas, yet the origin of sex-specific expression is unknown. Here, we used an in vitro differentiation model to convert human embryonic stem cells (hESCs) into trophoblastic progenitor cells of the first-trimester placenta, which will eventually become mature extravillous trophoblasts and syncytiotrophoblasts. We observed significant sex differences in transcriptomic profiles of hESCs and trophoblastic progenitors, and also with the differentiation process itself. Male cells had higher dosage of X/Y gene pairs relative to female samples, supporting functions for Y-linked genes beyond spermatogenesis in the hESCs and in the early placenta. Female-specific differentiation altered the expression of several thousand genes compared with male cells, and female cells specifically upregulated numerous autosomal genes with known roles in trophoblast function. Sex-biased upregulation of cellular pathways during trophoblast differentiation was also evident. This study is the first to identify sex differences in trophoblastic progenitor cells of the first-trimester human placenta, and reveal early origins for sexual dimorphism.

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Published In

cover image Stem Cells and Development
Stem Cells and Development
Volume 27Issue Number 19October 1, 2018
Pages: 1360 - 1375
PubMed: 29993333


Published in print: October 1, 2018
Published online: 20 September 2018
Published ahead of print: 21 August 2018
Published ahead of production: 11 July 2018
Accepted: 10 July 2018
Received: 13 April 2018


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Availability of Data and Material

RNA-Seq data sets have been deposited in the Gene Expression Omnibus (GEO) database (GSE115941).



Camille M. Syrett
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Isabel Sierra
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Corbett L. Berry
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Daniel Beiting
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Montserrat C. Anguera [email protected]
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.


Address correspondence to:Dr. Montserrat C. AngueraDepartment of Biomedical SciencesSchool of Veterinary MedicineUniversity of PennsylvaniaRoom 390EB3800 Spruce StreetPhiladelphia, PA 19104 [email protected]

Author Disclosure Statement

No competing financial interests exist.

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