Publication Date:
2013-07-23
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913367/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kueh, Hao Yuan -- Champhekar, Ameya -- Nutt, Stephen L -- Elowitz, Michael B -- Rothenberg, Ellen V -- R01 AI083514/AI/NIAID NIH HHS/ -- R01 CA090233/CA/NCI NIH HHS/ -- R01 CA90233/CA/NCI NIH HHS/ -- R33 HL089123/HL/NHLBI NIH HHS/ -- RC2 CA148278/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):670-3. doi: 10.1126/science.1240831. Epub 2013 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA, USA. kueh@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23868921" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Cycle/*genetics
;
Cell Differentiation/*genetics
;
Cells, Cultured
;
Feedback, Physiological
;
*Gene Expression Regulation
;
*Gene Regulatory Networks
;
Macrophages/cytology
;
Mice
;
Mice, Inbred Strains
;
Myeloid Cells/*cytology
;
Precursor Cells, B-Lymphoid/*cytology
;
Proto-Oncogene Proteins/genetics/*physiology
;
Trans-Activators/genetics/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
