Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation

Alexander Murray; Arnold R. Sienerth; Myriam Hemberger

doi:10.1038/srep25112

journal article Open Access Apr 28, 2016

Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation

Alexander Murray

Arnold R. Sienerth Myriam Hemberger

Scientific Reports Vol. 6 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep25112

Abstract

AbstractGene loci that are hypermethylated and repressed in embryonic (ESCs) but hypomethylated and expressed in trophoblast (TSCs) stem cells are very rare and may have particularly important roles in early developmental cell fate decisions, as previously shown for Elf5. Here, we assessed another member of this small group of genes, Placenta Expressed Transcript 1 (Plet1), for its function in establishing trophoblast lineage identity and modulating trophoblast differentiation. We find that Plet1 is tightly repressed by DNA methylation in ESCs but expressed on the cell surface of TSCs and trophoblast giant cells. In hypomethylated ESCs that are prone to acquire some trophoblast characteristics, Plet1 is required to confer a trophoblast-specific gene expression pattern, including up-regulation of Elf5. Plet1 displays an unusual biphasic expression profile during TSC differentiation and thus may be pivotal in balancing trophoblast self-renewal and differentiation. Furthermore, overexpression and CRISPR/Cas9-mediated knockout in TSCs showed that high Plet1 levels favour differentiation towards the trophoblast giant cell lineage, whereas lack of Plet1 preferentially induces syncytiotrophoblast formation. Thus, the endogenous dynamics of Plet1 expression establish important patterning cues within the trophoblast compartment by promoting differentiation towards the syncytiotrophoblast or giant cell pathway in Plet1-low and Plet1-high cells, respectively.

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Published: Apr 28, 2016
Vol/Issue: 6(1)
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Authors

A

Alexander Murray

Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Karlsruhe, Germany

Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada; Department of Medical Genetics, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada

Cite This Article

Alexander Murray, Arnold R. Sienerth, Myriam Hemberger (2016). Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation. Scientific Reports, 6(1). https://doi.org/10.1038/srep25112

Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation

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