Inheritance of OCT4 predetermines fate choice in human embryonic stem cells.

Autor: Wolff SC; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Kedziora KM; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Dumitru R; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Dungee CD; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Zikry TM; Department of Biostatistics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Beltran AS; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Haggerty RA; Curriculum for Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Cheng J; UNC Neuroscience Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Redick MA; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA., Purvis JE; Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA jeremy_purvis@med.unc.edu.; Curriculum for Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2018 Sep 03; Vol. 14 (9), pp. e8140. Date of Electronic Publication: 2018 Sep 03.
DOI: 10.15252/msb.20178140
Abstrakt: It is well known that clonal cells can make different fate decisions, but it is unclear whether these decisions are determined during, or before, a cell's own lifetime. Here, we engineered an endogenous fluorescent reporter for the pluripotency factor OCT4 to study the timing of differentiation decisions in human embryonic stem cells. By tracking single-cell OCT4 levels over multiple cell cycle generations, we found that the decision to differentiate is largely determined before the differentiation stimulus is presented and can be predicted by a cell's preexisting OCT4 signaling patterns. We further quantified how maternal OCT4 levels were transmitted to, and distributed between, daughter cells. As mother cells underwent division, newly established OCT4 levels in daughter cells rapidly became more predictive of final OCT4 expression status. These results imply that the choice between developmental cell fates can be largely predetermined at the time of cell birth through inheritance of a pluripotency factor.
(© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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