The molecular architecture of cell cycle arrest
Abstract The cellular decision governing the transition between proliferative and arrested states is crucial to the development and function of every tissue. While the molecular mechanisms that regulate the proliferative cell cycle are well established, we know comparatively little about what happen...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-09-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202211087 |
| _version_ | 1797281496247042048 |
|---|---|
| author | Wayne Stallaert Sovanny R Taylor Katarzyna M Kedziora Colin D Taylor Holly K Sobon Catherine L Young Juanita C Limas Jonah Varblow Holloway Martha S Johnson Jeanette Gowen Cook Jeremy E Purvis |
| author_facet | Wayne Stallaert Sovanny R Taylor Katarzyna M Kedziora Colin D Taylor Holly K Sobon Catherine L Young Juanita C Limas Jonah Varblow Holloway Martha S Johnson Jeanette Gowen Cook Jeremy E Purvis |
| author_sort | Wayne Stallaert |
| collection | DOAJ |
| description | Abstract The cellular decision governing the transition between proliferative and arrested states is crucial to the development and function of every tissue. While the molecular mechanisms that regulate the proliferative cell cycle are well established, we know comparatively little about what happens to cells as they diverge into cell cycle arrest. We performed hyperplexed imaging of 47 cell cycle effectors to obtain a map of the molecular architecture that governs cell cycle exit and progression into reversible (“quiescent”) and irreversible (“senescent”) arrest states. Using this map, we found multiple points of divergence from the proliferative cell cycle; identified stress‐specific states of arrest; and resolved the molecular mechanisms governing these fate decisions, which we validated by single‐cell, time‐lapse imaging. Notably, we found that cells can exit into senescence from either G1 or G2; however, both subpopulations converge onto a single senescent state with a G1‐like molecular signature. Cells can escape from this “irreversible” arrest state through the upregulation of G1 cyclins. This map provides a more comprehensive understanding of the overall organization of cell proliferation and arrest. |
| first_indexed | 2024-03-07T16:57:25Z |
| format | Article |
| id | doaj.art-cbb51f9db4bc4754b922f26991fa63c9 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:57:25Z |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-cbb51f9db4bc4754b922f26991fa63c92024-03-03T03:40:55ZengSpringer NatureMolecular Systems Biology1744-42922022-09-01189n/an/a10.15252/msb.202211087The molecular architecture of cell cycle arrestWayne Stallaert0Sovanny R Taylor1Katarzyna M Kedziora2Colin D Taylor3Holly K Sobon4Catherine L Young5Juanita C Limas6Jonah Varblow Holloway7Martha S Johnson8Jeanette Gowen Cook9Jeremy E Purvis10Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Biochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Biochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Biochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USAAbstract The cellular decision governing the transition between proliferative and arrested states is crucial to the development and function of every tissue. While the molecular mechanisms that regulate the proliferative cell cycle are well established, we know comparatively little about what happens to cells as they diverge into cell cycle arrest. We performed hyperplexed imaging of 47 cell cycle effectors to obtain a map of the molecular architecture that governs cell cycle exit and progression into reversible (“quiescent”) and irreversible (“senescent”) arrest states. Using this map, we found multiple points of divergence from the proliferative cell cycle; identified stress‐specific states of arrest; and resolved the molecular mechanisms governing these fate decisions, which we validated by single‐cell, time‐lapse imaging. Notably, we found that cells can exit into senescence from either G1 or G2; however, both subpopulations converge onto a single senescent state with a G1‐like molecular signature. Cells can escape from this “irreversible” arrest state through the upregulation of G1 cyclins. This map provides a more comprehensive understanding of the overall organization of cell proliferation and arrest.https://doi.org/10.15252/msb.202211087cell cycleproliferationquiescencesenescencesingle‐cell |
| spellingShingle | Wayne Stallaert Sovanny R Taylor Katarzyna M Kedziora Colin D Taylor Holly K Sobon Catherine L Young Juanita C Limas Jonah Varblow Holloway Martha S Johnson Jeanette Gowen Cook Jeremy E Purvis The molecular architecture of cell cycle arrest Molecular Systems Biology cell cycle proliferation quiescence senescence single‐cell |
| title | The molecular architecture of cell cycle arrest |
| title_full | The molecular architecture of cell cycle arrest |
| title_fullStr | The molecular architecture of cell cycle arrest |
| title_full_unstemmed | The molecular architecture of cell cycle arrest |
| title_short | The molecular architecture of cell cycle arrest |
| title_sort | molecular architecture of cell cycle arrest |
| topic | cell cycle proliferation quiescence senescence single‐cell |
| url | https://doi.org/10.15252/msb.202211087 |
| work_keys_str_mv | AT waynestallaert themoleculararchitectureofcellcyclearrest AT sovannyrtaylor themoleculararchitectureofcellcyclearrest AT katarzynamkedziora themoleculararchitectureofcellcyclearrest AT colindtaylor themoleculararchitectureofcellcyclearrest AT hollyksobon themoleculararchitectureofcellcyclearrest AT catherinelyoung themoleculararchitectureofcellcyclearrest AT juanitaclimas themoleculararchitectureofcellcyclearrest AT jonahvarblowholloway themoleculararchitectureofcellcyclearrest AT marthasjohnson themoleculararchitectureofcellcyclearrest AT jeanettegowencook themoleculararchitectureofcellcyclearrest AT jeremyepurvis themoleculararchitectureofcellcyclearrest AT waynestallaert moleculararchitectureofcellcyclearrest AT sovannyrtaylor moleculararchitectureofcellcyclearrest AT katarzynamkedziora moleculararchitectureofcellcyclearrest AT colindtaylor moleculararchitectureofcellcyclearrest AT hollyksobon moleculararchitectureofcellcyclearrest AT catherinelyoung moleculararchitectureofcellcyclearrest AT juanitaclimas moleculararchitectureofcellcyclearrest AT jonahvarblowholloway moleculararchitectureofcellcyclearrest AT marthasjohnson moleculararchitectureofcellcyclearrest AT jeanettegowencook moleculararchitectureofcellcyclearrest AT jeremyepurvis moleculararchitectureofcellcyclearrest |