Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation
- Author(s)
- Kueh, HY; Champhekhar, A; Nutt, SL; Elowitz, MB; Rothenberg, EV;
- Details
- Publication Year 2013-08-09,Volume 341,Issue #6146,Page 670-673
- Journal Title
- SCIENCE
- Publication Type
- Journal Article
- Abstract
- Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle-coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Keywords
- TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION; LEUKEMIA; PROGENITORS; FATES; MICE; PROLIFERATION; ACTIVATION; MACROPHAGE
- Research Division(s)
- Molecular Immunology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913367/
- Publisher's Version
- https://doi.org/10.1126/science.1240831
- Terms of Use/Rights Notice
- Copyright © 2013 American Association for the Advancement of Science. All Rights Reserved
Creation Date: 2013-08-09 12:00:00