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

Gene 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...

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Main Authors:	Murray, Alexander, Sienerth, Arnold R., Hemberger, Myriam
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848516/

id	pubmed-4848516
recordtype	oai_dc
spelling	pubmed-48485162016-05-05 Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation Murray, Alexander Sienerth, Arnold R. Hemberger, Myriam Article Gene 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. Nature Publishing Group 2016-04-28 /pmc/articles/PMC4848516/ /pubmed/27121762 http://dx.doi.org/10.1038/srep25112 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Murray, Alexander Sienerth, Arnold R. Hemberger, Myriam
spellingShingle	Murray, Alexander Sienerth, Arnold R. Hemberger, Myriam Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
author_facet	Murray, Alexander Sienerth, Arnold R. Hemberger, Myriam
author_sort	Murray, Alexander
title	Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
title_short	Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
title_full	Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
title_fullStr	Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
title_full_unstemmed	Plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
title_sort	plet1 is an epigenetically regulated cell surface protein that provides essential cues to direct trophoblast stem cell differentiation
description	Gene 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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848516/
_version_	1613572257327611904

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

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