Surviving apoptosis: life-death signaling in single cells
Deborah A Flusberg1, Peter K Sorger1
1Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
Tissue development and homeostasis are regulated by opposing pro-survival and pro-death signals. An interesting feature of the Tumor Necrosis Factor (TNF) family of ligands is that they simultaneously activate opposing signals within a single cell via the same ligand-receptor complex. The magnitude of pro-death events such as caspase activation and pro-survival events such as Nuclear Factor (NF)-κB activation vary not only from one cell type to the next but also among individual cells of the same type due to intrinsic and extrinsic noise. The molecules involved in these pro-survival and/or pro-death pathways, and the different phenotypes that result from their activities, have been recently reviewed. Here we focus on the impact of cell-to-cell variability in the strength of these opposing signals on shaping cell fate decisions.
Insights
Cellular fate decisions are shaped by variable pro-survival and pro-death signals from the Tumor Necrosis Factor (TNF) family. Understanding this cell-to-cell variability is key to tissue development and homeostasis.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Systems Biology
Background:
- Tissue development and homeostasis rely on a balance of pro-survival and pro-death signals.
- The Tumor Necrosis Factor (TNF) ligand family uniquely activates opposing intracellular signals simultaneously.
- Variability in signal strength, due to noise, influences cell fate decisions.
Purpose of the Study:
- To investigate the impact of cell-to-cell variability in opposing TNF-induced signals on cell fate.
- To understand how noise in signaling pathways affects cellular decisions.
Main Methods:
- Analysis of molecular pathways involved in pro-survival (e.g., Nuclear Factor-kappa B activation) and pro-death (e.g., caspase activation) signaling.
- Focus on cell-to-cell variability in signal strength within and between cell types.
Main Results:
- Cell-to-cell differences in signal magnitude lead to diverse cellular phenotypes.
- Variability in the balance of pro-survival and pro-death signals is a critical determinant of cell fate.
- Noise in signaling pathways contributes to the heterogeneity of cellular responses.
Conclusions:
- Cell-to-cell variability in TNF-mediated signaling significantly influences cell fate.
- Understanding signal noise is crucial for comprehending tissue homeostasis and development.
- The interplay between opposing signals and inherent cellular variability dictates cellular outcomes.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
01:30Apoptosis
01:31The Intrinsic Apoptotic Pathway
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...