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

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 de

SUBMITTER: Ahrends R 

PROVIDER: S-EPMC4733388 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature