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Network plasticity of pluripotency transcription factors in embryonic stem cells.
Nat. Cell Biol. 17, 1235-1246 (2015)
Transcription factor (TF) networks are thought to regulate embryonic stem cell (ESC) pluripotency. However, TF expression dynamics and regulatory mechanisms are poorly understood. We use reporter mouse ESC lines allowing non-invasive quantification of Nanog or Oct4 protein levels and continuous long-term single-cell tracking and quantification over many generations to reveal diverse TF protein expression dynamics. For cells with low Nanog expression, we identified two distinct colony types: one re-expressed Nanog in a mosaic pattern, and the other did not re-express Nanog over many generations. Although both expressed pluripotency markers, they exhibited differences in their TF protein correlation networks and differentiation propensities. Sister cell analysis revealed that differences in Nanog levels are not necessarily accompanied by differences in the expression of other pluripotency factors. Thus, regulatory interactions of pluripotency TFs are less stringently implemented in individual self-renewing ESCs than assumed at present.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
1465-7392
e-ISSN
1476-4679
Journal
Nature Cell Biology
Quellenangaben
Volume: 17,
Issue: 10,
Pages: 1235-1246
Publisher
Nature Publishing Group
Non-patent literature
Publications
Reviewing status
Peer reviewed