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• W2614043159 abstract "A fundamental challenge in cell biology is to understand how an individual cell commits to a particular fate1-3. A classic example is the fate decision between self-renewal and differentiation, which plays an essential role in the biology of human embryonic stem cells (hESCs)4. Despite significant advances in our understanding of development of the human embryo5,6, it is still unclear how, and when, an individual stem cell makes the decision to differentiate. Here, we used time-lapse fluorescence microscopy to capture differentiation of hESCs to trophoblast — the first cell fate decision during mammalian development. By tracing the histories of both self-renewing and differentiating cells, we found that each population displayed distinct levels of the pluripotency factor OCT4 long before they were exposed to a differentiation stimulus. The levels of OCT4 were lineage dependent; however, each mother cell distributed unequal levels of OCT4 to its daughter cells randomly during cell division. The resulting ratio of OCT4 between daughter cells — established immediately after division — determined downstream fates: cells receiving a greater ratio of maternal OCT4 showed sustained increases in OCT4 and a reduced capacity to differentiate. We propose a simple formula, pdaughter = (pmother)r, that successfully predicts the probability that a daughter cell will differentiate based on its mother cell's differentiation probability and its inherited ratio of OCT4. Our study reveals that the balance between self-renewal and differentiation is altered by the ratiometric distribution of OCT4 during cell division. These findings imply that a stem cell's fate is already largely determined by the time the cell is born." @default.
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• W2614043159 date "2017-05-12" @default.
• W2614043159 modified "2023-09-23" @default.
• W2614043159 title "Ratiometric Distribution Of OCT4 During Stem Cell Division Controls The Balance Between Self-Renewal And Differentiation" @default.
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• W2614043159 hasPublicationYear "2017" @default.
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