Molecular Competition in G1 Controls When Cells Simultaneously Commit to Terminally Differentiate and Exit the Cell Cycle
| Autor: | Michael L Zhao, Kyle M. Kovary, Atefeh Rabiee, Mary N. Teruel, Zahra Bahrami-Nejad, Brooks Taylor |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
terminal cell differentiation Cell cycle progression G1 lengthening Commit adipocyte General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Animals Humans Progenitor cell lcsh:QH301-705.5 Adipogenesis biology Mechanism (biology) Stem Cells Cell Cycle post-mitotic Gene Expression Regulation Developmental Cell Differentiation Cell cycle Cell biology 030104 developmental biology lcsh:Biology (General) Mitogen-activated protein kinase biology.protein cell cycle exit 030217 neurology & neurosurgery Cell Division |
| Zdroj: | Cell reports Cell Reports, Vol 31, Iss 11, Pp 107769-(2020) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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