ArticlePLoS computational biology2018
Quantitative single cell analysis uncovers the life/death decision in CD95 network.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Review
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- Arginine methylation of caspase-8 controls life/death decisions in extrinsic apoptotic networks.Oncogene · 2024Article
- Modulating the dynamics of NFκB and PI3K enhances the ensemble-level TNFR1 signaling mediated apoptotic response.NPJ systems biology and applications · 2023Article
- Current trends in luminescence-based assessment of apoptosis.RSC advances · 2023Review
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Modulation of signaling cross-talk between pJNK and pAKT generates optimal apoptotic response.PLoS computational biology · 2022Article
- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- Cell death in pancreatic cancer: from pathogenesis to therapy.Nature reviews. Gastroenterology & hepatology · 2021Review
- Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells.Scientific reports · 2021Article
- A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.The Journal of experimental medicine · 2021Article
- Theoretical study of the impact of adaptation on cell-fate heterogeneity and fractional killing.Scientific reports · 2020Article
- Interplay Between Mitophagy and Apoptosis Defines a Cell Fate Upon Co-treatment of Breast Cancer Cells With a Recombinant Fragment of Human κ-Casein and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand.Frontiers in cell and developmental biology · 2020Article
- Heterogeneous responses to low level death receptor activation are explained by random molecular assembly of the Caspase-8 activation platform.PLoS computational biology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD95/Fas/APO-1 is a member of the death receptor family that triggers apoptotic and anti-apoptotic responses in particular, NF-κB. These responses are characterized by a strong heterogeneity within a population of cells. To determine how the cell decides between life and death we developed a computational model supported by imaging flow cytometry analysis of CD95 signaling. Here we show that CD95 stimulation leads to the induction of caspase and NF-κB pathways simultaneously in one cell. The related life/death decision strictly depends on cell-to-cell variability in the formation of the death-inducing complex (DISC) on one side (extrinsic noise) vs. stochastic gene expression of the NF-κB pathway on the other side (intrinsic noise). Moreover, our analysis has uncovered that the stochasticity in apoptosis and NF-kB pathways leads not only to survival or death of a cell, but also causes a third type of response to CD95 stimulation that we termed ambivalent response. Cells in the ambivalent state can undergo cell death or survive which was subsequently validated by experiments. Taken together, we have uncovered how these two competing pathways control the fate of a cell, which in turn plays an important role for development of anti-cancer therapies.
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