Controlling low rates of cell differentiation through noise and ultrahigh feedback. Academic Article uri icon

Overview

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.

publication date

  • June 20, 2014

Research

keywords

  • Adipocytes
  • Adipogenesis
  • Models, Biological

Identity

PubMed Central ID

  • PMC4733388

Scopus Document Identifier

  • 84902667430

Digital Object Identifier (DOI)

  • 10.1126/science.1252079

PubMed ID

  • 24948735

Additional Document Info

volume

  • 344

issue

  • 6190