Controlling low rates of terminal cell differentiation through noise and ultra‐high feedback (981.1)
2014; Wiley; Volume: 28; Issue: S1 Linguagem: Inglês
10.1096/fasebj.28.1_supplement.981.1
ISSN1530-6860
AutoresMary N. Teruel, Robert Ahrends, Asuka Ota, Kyle M. Kovary, Byung Ouk Park,
Tópico(s)Single-cell and spatial transcriptomics
ResumoMammalian tissue size is maintained by slow replacement of aging cells. For adipocytes, key regulators of glucose and lipid metabolism, the renewal rate is only 10% per year. Here we use computational modeling, quantitative mass spectrometry (1) and single‐cell microscopy (2) to show that expression noise acts within a network of more than six positive feedbacks to permit pre‐adipocytes to differentiate at very low rates. This solves two fundamental opposing requirements: high cell‐to‐cell signal variability generates very low differentiation rates while low signal variability keeps cells irreversibly locked in the differentiated state. Thus, the challenge of how higher eukaryotes control low rates of irreversible cell fate decisions can be solved by a balancing act between expression noise and ultra‐high feedback connectivity. (1) Abell E,…, Teruel MN (2011). Proc Natl Acad Sci U S A. Aug 30; 108(35):14485‐90. (2) Park BO,…, Teruel MN. (2012). Cell Reports 2012 Oct 25. PMID: 23063366.
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