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1.
Mol Syst Biol ; 18(9): e11087, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36161508

RESUMO

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.


Assuntos
Ciclinas , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Divisão Celular , Proliferação de Células , Ciclinas/genética , Ciclinas/metabolismo
2.
Cell Syst ; 13(3): 230-240.e3, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-34800361

RESUMO

Understanding the organization of the cell cycle has been a longstanding goal in cell biology. We combined time-lapse microscopy, highly multiplexed single-cell imaging of 48 core cell cycle proteins, and manifold learning to render a visualization of the human cell cycle. This data-driven approach revealed the comprehensive "structure" of the cell cycle: a continuum of molecular states that cells occupy as they transition from one cell division to the next, or as they enter or exit cell cycle arrest. Paradoxically, progression deeper into cell cycle arrest was accompanied by increases in proliferative effectors such as CDKs and cyclins, which can drive cell cycle re-entry by overcoming p21 induction. The structure also revealed the molecular trajectories into senescence and the unique combination of molecular features that define this irreversibly arrested state. This approach will enable the comparison of alternative cell cycles during development, in response to environmental perturbation and in disease. A record of this paper's transparent peer review process is included in the supplemental information.


Assuntos
Quinases Ciclina-Dependentes , Ciclinas , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Divisão Celular , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Humanos
3.
J Am Mosq Control Assoc ; 24(3): 450-2, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18939701

RESUMO

The checklist of the mosquito species reported to occur in the state of Indiana is updated to include a number of new records and new classifications. Specimens of the cryptic species complex Anopheles quadrimaculatus s.1. are identified as An. quadrimaculatus s.s., and specimens of An. punctipennis are identified as the Eastern form of the species.


Assuntos
Anopheles/classificação , Animais , Indiana
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