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

被引：445

作者：

Goolam, Mubeen ^{[1
]}

Scialdone, Antonio ^{[2
,3
]}

Graham, Sarah J. L. ^{[1
]}

Macaulay, Iain C. ^{[3
]}

Jedrusik, Agnieszka ^{[1
]}

Hupalowska, Anna ^{[1
]}

Voet, Thierry ^{[3
,4
]}

Marioni, John C. ^{[2
,3
,5
]}

Zernicka-Goetz, Magdalena ^{[1
]}

机构：

[1] Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England

[2] European Bioinformat Inst, EMBL, Wellcome Genome Campus, Cambridge CB10 1SD, England

[3] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England

[4] Katholieke Univ Leuven, Dept Human Genet, Lab Reprod Genom, Herestr 49, B-3000 Leuven, Belgium

[5] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

来源：

CELL | 2016年 / 165卷 / 01期

基金：

英国惠康基金;

关键词：

RNA-SEQ; REGULATES PLURIPOTENCY; SPATIAL ARRANGEMENT; GENE-EXPRESSION; TROPHECTODERM; BLASTOMERES; CLEAVAGE; MASS; DIFFERENTIATION; SPECIFICATION;

D O I：

10.1016/j.cell.2016.01.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 followig 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 expressionn, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation.

引用

页码：61 / 74

页数：14

共 46 条

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