Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 29, 2024

Abstract Random fluctuations (noise) in gene expression can be studied from two complementary perspectives: following a single cell over time or comparing between cells proliferating population at given time. Here, we systematically investigated scenarios where both perspectives lead to different levels of noise product. We first consider stable protein, whose concentration is diluted by cellular growth, and the protein inhibits growth high concentrations, establishing positive feedback loop. For stochastic model with molecular bursting products, analytically predict contrast steady-state distributions frameworks. Although amplifies expression, this amplification much higher framework compared also study other processes that even absence such dilution-based feedback. When considering randomness partitioning molecules daughters during mitosis, find single-cell perspective, independent cycle duration. In contrast, amplified perspective increasing cell-cycle Overall, our results show commonly used does not account for can, some cases, underestimate product levels. These have important implications studying inter-cellular variation stress-related programs across types are known inhibit growth.

Language: Английский

---

Intracellular diffusion in the cytoplasm increases with cell size in fission yeast

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

ABSTRACT Diffusion in the cytoplasm can greatly impact cellular processes, yet regulation of macromolecular diffusion remains poorly understood. There is increasing evidence that cell size affects density and composition cytoplasm. Here, we studied whether at scale macromolecules tens microns diameter. We analyzed diffusive motions intracellular genetically-encoded multimeric 40 nm nanoparticles (cytGEMs) fission yeast Schizosaccharomyces pombe . Using mutants, showed cytGEMs coefficients decreased smaller cells increased larger cells. This increase large may be due to a decrease DNA-to-Cytoplasm ratio, as was not affected multinucleate cytokinesis mutants. In investigating underlying causes altered diffusion, found proteomes small exhibited size-specific changes, including sub-scaling ribosomal proteins Comparison with similar dataset from human revealed features size-dependent proteome remodeling were conserved. These studies demonstrate an important parameter determining biophysical properties

Language: Английский

---

Nuclear Entry of DNA and Transgene Expression in Dividing and Non-dividing Cells

Cellular and Molecular Bioengineering, Journal Year: 2023, Volume and Issue: 16(5-6), P. 459 - 474

Published: Sept. 17, 2023

Language: Английский

---

The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(22)

Published: Nov. 3, 2023

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response signals. Despite being growth factor, FGF2 has antiproliferative tumor-suppressive functions some contexts. In this work, we investigated how the effect modulates chromatin-, nucleolus- rDNA-associated proteins. chromatin nucleolar proteome indicated that stimulation proteins related transcription, rRNA expression chromatin-remodeling global transcriptional rate area increased along with disorganization upon 24 h stimulation. induced immature accumulation by increasing transcription. protein analysis reinforced stimulus interferes transcription processing. RNA Pol I inhibition partially reversed arrest FGF2, indicating changes might be crucial for triggering effect. Taken together, demonstrate triggers significant main cell site, nucleolus.

Language: Английский

---

Gene expression in growing cells: A biophysical primer

arXiv (Cornell University), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Cell growth and gene expression, essential elements of all living systems, have long been the focus biophysical interrogation. Advances in single-cell methods invigorated theoretical studies into these processes. However, until recently, there was little dialog between two areas study. Most models for regulation assumed activity to be oblivious progression cell cycle birth division. But are numerous ways which periodic character cellular observables can modulate expression. The molecular factors required transcription translation increase number during cycle, but also diluted due continuous volume. replication genome changes dosage those same players provides competing targets regulatory binding. Finally, division reduces their again, so forth. Stochasticity is inherent biological processes, manifested fluctuations synthesis degradation new components as well random partitioning molecules at each notion expression stationary thus hard justify. In this review, we survey emerging paradigm cell-cycle regulated with an emphasis on global patterns rather than gene-specific regulation. We discuss recent experimental reports where were simultaneously measured individual cells, providing first glimpses coupling two. While findings, not surprisingly, differ among genes organisms, several emerged that attempt reconcile differences form a unifying framework understanding growing cells.

Language: Английский

---

Influence of cell volume on the gene transcription rate

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2024, Volume and Issue: 1867(1), P. 195008 - 195008

Published: Jan. 19, 2024

Language: Английский

---

Constant surface area-to-volume ratio during cell growth as a design principle in mammalian cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

ABSTRACT All cells are subject to geometric constraints, such as surface area-to-volume (SA/V) ratio, that impact cell functions and force biological adaptations. Like the SA/V ratio of a sphere, it is generally assumed decreases size increases. Here, we investigate this in near-spherical mammalian using single-cell measurements mass proteins, well imaging plasma membrane morphology. We find remains surprisingly constant grow larger. This observation largely independent cycle amount growth. Consequently, growth results increased folding, which simplifies cellular design by ensuring sufficient area for division, nutrient uptake deformation at all sizes.

Language: Английский

---

Colloquium : Gene expression in growing cells: A biophysical primer

Reviews of Modern Physics, Journal Year: 2024, Volume and Issue: 96(4)

Published: Oct. 4, 2024

Language: Английский

---