Document Type

Article

Publication Title

Cell Reports

ISSN

2211-1247

Volume

31

Issue

11

DOI

10.1016/j.celrep.2020.107769

Publication Date

6-16-2020

Abstract

Terminal differentiation is essential for the development and maintenance of tissues in all multi-cellular organisms and is associated with permanent exit from the cell cycle. Failure to permanently exit the cell cycle can result in cancer and disease. However, the molecular mechanisms and timing that coordinate differentiation commitment and cell cycle exit are not yet understood. Using live, single-cell imaging of cell cycle progression and differentiation commitment during adipogenesis, we show that a rapid switch mechanism engages exclusively in G1 to trigger differentiation commitment simultaneously with permanent exit from the cell cycle. We identify a molecular competition in G1 between when the differentiation switch is triggered and when the proliferative window closes that allows mitogen and differentiation stimuli to control the balance between terminally differentiating cells produced and progenitor cells kept in reserve, a parameter of critical importance for enabling proper development of tissue domains and organs. Zhao et al. show that in terminally differentiating cells, a rapid switch mechanism engages exclusively during a G1 period to trigger simultaneous differentiation commitment and permanent cell cycle exit. A molecular competition in each G1 period allows cells to control the balance the terminally differentiating cells produced and progenitor cells kept in reserve.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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