Open AccessInheritance of OCT 4 predetermines fate choice in human embryonic stem cells
Author(s) -
Wolff Samuel C,
Kedziora Katarzyna M,
Dumitru Raluca,
Dungee Cierra D,
Zikry Tarek M,
Beltran Adriana S,
Haggerty Rachel A,
Cheng JrGang,
Redick Margaret A,
Purvis Jeremy E
Publication year - 2018
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20178140
Subject(s) - chapel , history , art history
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 OCT 4 to study the timing of differentiation decisions in human embryonic stem cells. By tracking single‐cell OCT 4 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 OCT 4 signaling patterns. We further quantified how maternal OCT 4 levels were transmitted to, and distributed between, daughter cells. As mother cells underwent division, newly established OCT 4 levels in daughter cells rapidly became more predictive of final OCT 4 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.