Sex-dependent gene expression in human pluripotent stem cells

Daniel Ronen, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Males and females have a variety of sexually dimorphic traits, most of which result from hormonal differences. However, differences between male and female embryos initiate very early in development, before hormonal influence begins, suggesting the presence of genetically driven sexual dimorphisms. By comparing the gene expression profiles of male and X-inactivated female human pluripotent stem cells, we detected Y-chromosome-driven effects. We discovered that the sex-determining gene SRY is expressed in human male pluripotent stem cells and is induced by reprogramming. In addition, we detected more than 200 differentially expressed autosomal genes in male and female embryonic stem cells. Some of these genes are involved in steroid metabolism pathways and lead to sex-dependent differentiation in response to the estrogen precursor estrone. Thus, we propose that the presence of the Ychromosome and specifically SRY may drive sex-specific differences in the growth and differentiation of pluripotent stem cells.

Original languageAmerican English
Pages (from-to)923-932
Number of pages10
JournalCell Reports
Issue number4
StatePublished - 21 Aug 2014

Bibliographical note

Funding Information:
The authors would like to thank Vadim Gercenstein for his assistance with the experiments and Tamar Golan-Lev for her assistance with the graphic design. We also wish to thank Tal Bruck, Uri Ben-David and Yonatan Stelzer for critical readings of the manuscript. This research was partially funded by the Israel Science Foundation-Morasha Foundation (1252/12), the Israel Ministry of Science and Technology Infrastructure (3-9693), and the Rosetrees Trust. D.R. is supported by the Israel Cancer Research Fund (ICRF) and the Lady Davis Fellowship Trust. N.B. holds the Herbert Cohn Chair in Cancer Research.


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