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Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation
Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201284/ https://www.ncbi.nlm.nih.gov/pubmed/25319825 http://dx.doi.org/10.1101/gad.247163.114 |
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author | Rhee, Catherine Lee, Bum-Kyu Beck, Samuel Anjum, Azeen Cook, Kendra R. Popowski, Melissa Tucker, Haley O. Kim, Jonghwan |
author_facet | Rhee, Catherine Lee, Bum-Kyu Beck, Samuel Anjum, Azeen Cook, Kendra R. Popowski, Melissa Tucker, Haley O. Kim, Jonghwan |
author_sort | Rhee, Catherine |
collection | PubMed |
description | Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell self-renewal and pluripotency, few TE-specific regulators have been identified, thereby limiting our understanding of mechanisms underlying the first cell fate decision. Here we show that up-regulation and nuclear entry of AT-rich interactive domain 3a (Arid3a) drives TE-like transcriptional programs in ES cells, maintains trophoblast stem (TS) cell self-renewal, and promotes further trophoblastic differentiation both upstream and independent of Cdx2. Accordingly, Arid3a(−/−) mouse post-implantation placental development is severely impaired, resulting in early embryonic death. We provide evidence that Arid3a directly activates TE-specific and trophoblast lineage-specific genes while directly repressing pluripotency genes via differential regulation of epigenetic acetylation or deacetylation. Our results identify Arid3a as a critical regulator of TE and placental development through execution of the commitment and differentiation phases of the first cell fate decision. |
format | Online Article Text |
id | pubmed-4201284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42012842014-10-22 Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation Rhee, Catherine Lee, Bum-Kyu Beck, Samuel Anjum, Azeen Cook, Kendra R. Popowski, Melissa Tucker, Haley O. Kim, Jonghwan Genes Dev Research Paper Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell self-renewal and pluripotency, few TE-specific regulators have been identified, thereby limiting our understanding of mechanisms underlying the first cell fate decision. Here we show that up-regulation and nuclear entry of AT-rich interactive domain 3a (Arid3a) drives TE-like transcriptional programs in ES cells, maintains trophoblast stem (TS) cell self-renewal, and promotes further trophoblastic differentiation both upstream and independent of Cdx2. Accordingly, Arid3a(−/−) mouse post-implantation placental development is severely impaired, resulting in early embryonic death. We provide evidence that Arid3a directly activates TE-specific and trophoblast lineage-specific genes while directly repressing pluripotency genes via differential regulation of epigenetic acetylation or deacetylation. Our results identify Arid3a as a critical regulator of TE and placental development through execution of the commitment and differentiation phases of the first cell fate decision. Cold Spring Harbor Laboratory Press 2014-10-15 /pmc/articles/PMC4201284/ /pubmed/25319825 http://dx.doi.org/10.1101/gad.247163.114 Text en © 2014 Rhee et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Rhee, Catherine Lee, Bum-Kyu Beck, Samuel Anjum, Azeen Cook, Kendra R. Popowski, Melissa Tucker, Haley O. Kim, Jonghwan Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title | Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title_full | Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title_fullStr | Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title_full_unstemmed | Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title_short | Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
title_sort | arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201284/ https://www.ncbi.nlm.nih.gov/pubmed/25319825 http://dx.doi.org/10.1101/gad.247163.114 |
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