Molecular control of cell density-mediated exit to quiescence
Summary: Contact inhibition of cell proliferation regulates tissue size and prevents uncontrolled cell expansion. When cell density increases, contact inhibition can force proliferating cells into quiescence. Here we show that the variable memory of local cell density experienced by a mother cell co...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721008536 |
| _version_ | 1818643255320903680 |
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| author | Yilin Fan Tobias Meyer |
| author_facet | Yilin Fan Tobias Meyer |
| author_sort | Yilin Fan |
| collection | DOAJ |
| description | Summary: Contact inhibition of cell proliferation regulates tissue size and prevents uncontrolled cell expansion. When cell density increases, contact inhibition can force proliferating cells into quiescence. Here we show that the variable memory of local cell density experienced by a mother cell controls the levels of the cyclin-dependent kinase (CDK) activator cyclin D1 and inhibitor p27 in newborn daughters, which direct cells to proliferation or quiescence. Much of this regulation can be explained by rapid suppression of ERK activity by high cell density in mothers, which leads to lower cyclin D1 and higher p27 levels in daughters. Strikingly, cell density and mitogen signals compete by shifting the ratio of cyclin D1/p27 levels below or above a single sharp threshold that controls the proliferation decision. Thus, the history of competing cell density and mitogen signals experienced by mothers is funneled into a precise activator-inhibitor balance that decides the fate of daughter cells. |
| first_indexed | 2024-12-16T23:56:03Z |
| format | Article |
| id | doaj.art-c52d915224474252a1209b7fc384479c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T23:56:03Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c52d915224474252a1209b7fc384479c2022-12-21T22:11:13ZengElsevierCell Reports2211-12472021-07-01364109436Molecular control of cell density-mediated exit to quiescenceYilin Fan0Tobias Meyer1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USADepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding authorSummary: Contact inhibition of cell proliferation regulates tissue size and prevents uncontrolled cell expansion. When cell density increases, contact inhibition can force proliferating cells into quiescence. Here we show that the variable memory of local cell density experienced by a mother cell controls the levels of the cyclin-dependent kinase (CDK) activator cyclin D1 and inhibitor p27 in newborn daughters, which direct cells to proliferation or quiescence. Much of this regulation can be explained by rapid suppression of ERK activity by high cell density in mothers, which leads to lower cyclin D1 and higher p27 levels in daughters. Strikingly, cell density and mitogen signals compete by shifting the ratio of cyclin D1/p27 levels below or above a single sharp threshold that controls the proliferation decision. Thus, the history of competing cell density and mitogen signals experienced by mothers is funneled into a precise activator-inhibitor balance that decides the fate of daughter cells.http://www.sciencedirect.com/science/article/pii/S2211124721008536cell cyclecell proliferationquiescencecell densitycontact inhibitionCDK |
| spellingShingle | Yilin Fan Tobias Meyer Molecular control of cell density-mediated exit to quiescence Cell Reports cell cycle cell proliferation quiescence cell density contact inhibition CDK |
| title | Molecular control of cell density-mediated exit to quiescence |
| title_full | Molecular control of cell density-mediated exit to quiescence |
| title_fullStr | Molecular control of cell density-mediated exit to quiescence |
| title_full_unstemmed | Molecular control of cell density-mediated exit to quiescence |
| title_short | Molecular control of cell density-mediated exit to quiescence |
| title_sort | molecular control of cell density mediated exit to quiescence |
| topic | cell cycle cell proliferation quiescence cell density contact inhibition CDK |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721008536 |
| work_keys_str_mv | AT yilinfan molecularcontrolofcelldensitymediatedexittoquiescence AT tobiasmeyer molecularcontrolofcelldensitymediatedexittoquiescence |