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Science. 2014 Jun 20;344(6190):1384-9. doi: 10.1126/science.1252079.

Controlling low rates of cell differentiation through noise and ultrahigh feedback.

Author information

1
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
2
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA. mteruel@stanford.edu.

Abstract

Mammalian tissue size is maintained by slow replacement of de-differentiating and dying cells. For adipocytes, key regulators of glucose and lipid metabolism, the renewal rate is only 10% per year. We used computational modeling, quantitative mass spectrometry, and single-cell microscopy to show that cell-to-cell variability, or noise, in protein abundance acts within a network of more than six positive feedbacks to permit pre-adipocytes to differentiate at very low rates. This reconciles two fundamental opposing requirements: High cell-to-cell signal variability is needed to generate very low differentiation rates, whereas low signal variability is needed to prevent differentiated cells from de-differentiating. Higher eukaryotes can thus control low rates of near irreversible cell fate decisions through a balancing act between noise and ultrahigh feedback connectivity.

PMID:
24948735
PMCID:
PMC4733388
DOI:
10.1126/science.1252079
[Indexed for MEDLINE]
Free PMC Article

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