Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos

The major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterize transcriptomes of all individual cells throughout mouse pre-implantation development....

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Main Authors:	Goolam, Mubeen, Scialdone, Antonio, Graham, Sarah J.L., Macaulay, Iain C., Jedrusik, Agnieszka, Hupalowska, Anna, Voet, Thierry, Marioni, John C., Zernicka-Goetz, Magdalena
Format:	Online
Language:	English
Published:	Cell Press 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819611/

id	pubmed-4819611
recordtype	oai_dc
spelling	pubmed-48196112016-04-14 Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos Goolam, Mubeen Scialdone, Antonio Graham, Sarah J.L. Macaulay, Iain C. Jedrusik, Agnieszka Hupalowska, Anna Voet, Thierry Marioni, John C. Zernicka-Goetz, Magdalena Article The major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterize transcriptomes of all individual cells throughout mouse pre-implantation development. This identifies targets of master pluripotency regulators Oct4 and Sox2 as being highly heterogeneously expressed between blastomeres of the 4-cell embryo, with Sox21 showing one of the most heterogeneous expression profiles. Live-cell tracking demonstrates that cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21 results in premature upregulation of the differentiation regulator Cdx2, suggesting that Sox21 helps safeguard pluripotency. Furthermore, Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1 and is lowered following CARM1 inhibition, indicating the importance of epigenetic regulation. Therefore, our results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation. Cell Press 2016-03-24 /pmc/articles/PMC4819611/ /pubmed/27015307 http://dx.doi.org/10.1016/j.cell.2016.01.047 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (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	Goolam, Mubeen Scialdone, Antonio Graham, Sarah J.L. Macaulay, Iain C. Jedrusik, Agnieszka Hupalowska, Anna Voet, Thierry Marioni, John C. Zernicka-Goetz, Magdalena
spellingShingle	Goolam, Mubeen Scialdone, Antonio Graham, Sarah J.L. Macaulay, Iain C. Jedrusik, Agnieszka Hupalowska, Anna Voet, Thierry Marioni, John C. Zernicka-Goetz, Magdalena Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
author_facet	Goolam, Mubeen Scialdone, Antonio Graham, Sarah J.L. Macaulay, Iain C. Jedrusik, Agnieszka Hupalowska, Anna Voet, Thierry Marioni, John C. Zernicka-Goetz, Magdalena
author_sort	Goolam, Mubeen
title	Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
title_short	Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
title_full	Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
title_fullStr	Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
title_full_unstemmed	Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos
title_sort	heterogeneity in oct4 and sox2 targets biases cell fate in 4-cell mouse embryos
description	The major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterize transcriptomes of all individual cells throughout mouse pre-implantation development. This identifies targets of master pluripotency regulators Oct4 and Sox2 as being highly heterogeneously expressed between blastomeres of the 4-cell embryo, with Sox21 showing one of the most heterogeneous expression profiles. Live-cell tracking demonstrates that cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21 results in premature upregulation of the differentiation regulator Cdx2, suggesting that Sox21 helps safeguard pluripotency. Furthermore, Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1 and is lowered following CARM1 inhibition, indicating the importance of epigenetic regulation. Therefore, our results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation.
publisher	Cell Press
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819611/
_version_	1613561712773955584

Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos

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