GO:0009409 response to cold: Cellular Stress Response, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0009409 response to cold is defined as any process that results in a change in state or activity of a cell or an organism as a result of a cold stimulus, a temperature below the optimal temperature for that organism.
• The response to cold is an evolutionarily conserved biological process that operates across taxa, from plants and zebrafish to pigs and humans.
• In mammals, cold stress triggers transcriptional and metabolic reprogramming in skeletal muscle and alters social and locomotor behaviors.
• In plants, cold stress activates complex regulatory networks that overlap with drought responses, involving transcription factors and signaling cascades.
• Human cold-related phenotypes include susceptibility to the common cold, which is modulated by psychological stress and social factors.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal dissection of genes annotated to GO:0009409.
Description
GO:0009409 response to cold is a biological process ontology term that describes any process resulting in a change in state or activity of a cell or an organism as a result of a cold stimulus, defined as a temperature below the optimal temperature for that organism. This term captures a wide range of physiological, cellular, and molecular responses, from immediate cold-shock protein induction to long-term acclimation and behavioral adaptation. Understanding response to cold is critical because temperature is a fundamental environmental variable that shapes organismal survival, geographic distribution, and disease susceptibility. In biomedical research, cold stress responses are relevant to metabolic physiology, neurobehavioral adaptation, and immune function. In plant science, cold response pathways are central to crop resilience and overlap with drought signaling networks. The breadth of GO:0009409 makes it a powerful annotation for comparative and functional genomics, enabling researchers to identify conserved and lineage-specific cold-adaptive mechanisms.
response to cold At A Glance
| GO ID | GO:0009409 |
|---|---|
| GO term | response to cold |
| Ontology | biological_process |
| Synonym | freezing tolerance |
| Definition | Any process that results in a change in state or activity of a cell or an organism as a result of a cold stimulus, a temperature stimulus below the optimal temperature for that organism. |
| Major function | Coordinated cellular and organismal adaptation to suboptimal low temperatures, including gene expression changes, metabolic adjustments, and behavioral responses. |
| Taxonomic scope | Conserved across plants, animals, and other organisms; experimentally studied in pig, zebrafish, Arabidopsis, and human models. |
| Related disease relevance | Common cold susceptibility, cold-stress-related metabolic and behavioral phenotypes. |
What Is GO:0009409?
GO:0009409 response to cold is defined by QuickGO as any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cold stimulus, a temperature stimulus below the optimal temperature for that organism. The term is synonymous with freezing tolerance in some contexts. It is a biological process term that encompasses molecular, cellular, and systemic reactions to cold, including transcriptional reprogramming, metabolic shifts, and behavioral adjustments.
Why Is response to cold Important in Cell Biology?
GO:0009409 response to cold is important because cold is a pervasive environmental stressor that affects organismal fitness, agricultural productivity, and human health. In livestock such as pigs, cold stress alters skeletal muscle gene expression and metabolism, with implications for meat quality and animal welfare. In plants, cold response networks are critical for freezing tolerance and are intertwined with drought signaling, making them targets for crop improvement. In humans, cold-related conditions such as the common cold are influenced by psychological stress and social factors, highlighting the intersection of environmental temperature, behavior, and immune function. In zebrafish, acute cold stress alters social behaviors, providing a model for neurobehavioral cold adaptation. Thus, understanding the molecular and physiological basis of response to cold has broad relevance across medicine, agriculture, and ecology.
• Cold stress is a major determinant of crop yield and geographic range in plants.
• In pigs, cold stress affects skeletal muscle transcriptome and metabolic pathways, impacting meat production.
• Zebrafish exhibit altered social behaviors under acute cold stress, linking temperature to neurobehavior.
• Human susceptibility to the common cold is modulated by psychological stress and social ties.
• Cold response pathways overlap with drought signaling networks in plants, enabling cross-tolerance engineering.
• GO:0009409 annotations facilitate comparative genomics of thermal adaptation across species.
• Cold stress responses involve conserved cold-shock proteins and transcription factors.
• Understanding cold response can inform therapeutic strategies for cold-related human conditions.
• CRISPR models allow causal testing of genes annotated to GO:0009409.
• Cold acclimation mechanisms are relevant to conservation and climate adaptation research.
What Happens During response to cold?
Cold sensing and signal transduction
In simple terms: Cells first detect that it is getting cold and send signals to switch on protective programs.
In plants, cold stress is sensed and transduced through calcium signaling, membrane fluidity changes, and activation of transcription factors such as CBF/DREB1, which orchestrate cold-responsive gene expression. In mammals, cold exposure activates thermosensory pathways and sympathetic nervous system responses that alter gene expression in tissues such as skeletal muscle. In zebrafish, acute cold stress triggers neuroendocrine signaling that modifies social behavior.
Transcriptional reprogramming
In simple terms: The cell changes which genes are turned on or off to cope with cold.
Cold stress induces large-scale changes in gene expression. In Min pig skeletal muscle, cold stress alters the expression of genes involved in energy metabolism, muscle contraction, and stress response. In plants, cold stress activates a regulatory network that includes CBF transcription factors and their target cold-regulated (COR) genes, which overlap with drought-responsive pathways.
Metabolic and physiological adjustments
In simple terms: The organism shifts its metabolism to generate heat and protect tissues.
Cold exposure increases energy expenditure and alters lipid and carbohydrate metabolism. In pigs, cold stress affects skeletal muscle metabolic pathways, potentially influencing meat quality. In plants, cold acclimation involves accumulation of cryoprotectants such as soluble sugars and proline, and remodeling of membrane lipids to maintain fluidity.
Behavioral responses
In simple terms: Animals change their behavior to avoid or cope with cold.
Zebrafish under acute cold stress show altered social behaviors, including changes in shoaling and aggression, which are thought to be adaptive. In humans, cold perception influences social behavior and susceptibility to the common cold, with psychological stress and social ties modulating risk.
Acclimation and tolerance
In simple terms: With repeated cold exposure, organisms can become more tolerant.
Cold acclimation in plants involves sustained expression of COR genes and accumulation of protective proteins, leading to increased freezing tolerance. In animals, repeated cold exposure can induce metabolic and behavioral adaptations, although the molecular basis is less characterized.
Key Genes Involved in GO:0009409 response to cold
The following genes and proteins have been experimentally implicated in response to cold (GO:0009409) across plant and animal models.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CBF1/DREB1B | Cold-responsive transcription factor in plants | Central regulator of cold acclimation and freezing tolerance |
| CBF2/DREB1C | Cold-responsive transcription factor in plants | Paralogous regulator of COR gene expression |
| CBF3/DREB1A | Cold-responsive transcription factor in plants | Key activator of cold-regulated genes |
| COR15A | Cold-regulated protein in plants | Protects chloroplast membranes during freezing |
| ICE1 | Upstream regulator of CBF expression in plants | Controls cold-induced CBF pathway |
| HSP70 | Heat shock protein with cold-protective roles | Molecular chaperone induced by cold stress |
| MYB15 | Negative regulator of CBF expression in plants | Modulates cold tolerance |
| ZAT12 | Zinc finger transcription factor in plants | Regulates cold-responsive gene network |
| SFR6 | Regulator of cold acclimation in plants | Affects COR gene expression |
| LOS1 | Translational regulator in plants | Required for cold acclimation |
| FAD2 | Fatty acid desaturase in plants | Alters membrane lipid composition for cold tolerance |
| PP2C | Protein phosphatase in cold signaling | Modulates cold-responsive kinase pathways |
| OST1 | Protein kinase in cold signaling | Activates cold-responsive transcription factors |
| MYC2 | Transcription factor in cold and drought crosstalk | Integrates cold and drought signals |
| NCED3 | Abscisic acid biosynthesis gene | Induced by cold and drought |
| P5CS1 | Proline biosynthesis gene | Accumulates proline during cold acclimation |
| SOD | Superoxide dismutase | Antioxidant defense during cold stress |
| CAT | Catalase | Antioxidant defense during cold stress |
How Is response to cold Regulated?
The response to cold (GO:0009409) is regulated at multiple levels. In plants, the CBF/DREB1 pathway is a central regulatory hub, controlled by upstream transcription factors such as ICE1 and negative regulators like MYB15, and modulated by protein phosphorylation and ubiquitination. Cold signaling also intersects with abscisic acid (ABA) and drought pathways, enabling cross-regulation. In animals, cold stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, leading to changes in gene expression and metabolism. In zebrafish, cold stress alters neuroendocrine signaling that modulates social behavior. In humans, psychological stress and social factors can modulate susceptibility to the common cold, indicating higher-order regulation of cold-related outcomes.
response to cold and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CBF1/DREB1B | Plant freezing tolerance | Arabidopsis knockout and overexpression lines |
| ICE1 | Cold acclimation in plants | Arabidopsis point mutation and knockout |
| HSP70 | Cold stress response in muscle | Pig skeletal muscle cell knockout |
| SOD | Oxidative stress during cold | Zebrafish knockout |
| MYB15 | Negative regulation of cold tolerance | Plant overexpression and knockout |
Common cold susceptibility
The common cold is a viral infection whose susceptibility is influenced by environmental and psychological factors. Psychological stress and social ties have been shown to modulate the risk of developing the common cold in human studies. While the common cold is not directly caused by cold temperature, the response to cold (GO:0009409) may interact with immune function and behavioral factors that influence infection risk.
Cold stress in livestock and metabolic health
In pigs, cold stress alters skeletal muscle gene expression and metabolic pathways, which can affect meat quality and animal health. These findings have implications for livestock management and for understanding metabolic responses to cold in mammals.
Neurobehavioral effects of cold stress
Zebrafish exposed to acute cold stress exhibit altered social behaviors, providing a model for understanding how cold temperature affects neurobehavioral processes. This has relevance for understanding cold-related behavioral changes in other species, including humans.
From response to cold-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CBF1 knockout reduce freezing tolerance? | Arabidopsis knockout |
| Does a point mutation in ICE1 alter cold-responsive gene expression? | Arabidopsis point mutation |
| Does overexpression of COR15A enhance cold tolerance? | Plant overexpression |
| Does HSP70 knockout affect cold-stress survival in muscle cells? | Pig skeletal muscle cell knockout |
| Does SOD knockout alter oxidative stress under cold? | Zebrafish knockout |
| Does tagged CBF1 knock-in reveal dynamic localization? | Plant tagged knock-in |
How to Study the response to cold Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Cold stress transcriptomics in pig muscle and plants |
| Proteomics | Protein abundance and modifications | Cold acclimation protein profiling |
| Metabolomics | Metabolite levels | Cryoprotectant accumulation during cold acclimation |
| Behavioral tracking | Social and locomotor behavior | Zebrafish cold stress response |
| CRISPR knockout | Loss-of-function phenotypes | Testing cold-responsive gene function |
| CRISPR point mutation | Specific amino acid function | Dissecting signaling protein domains |
| CRISPR knock-in | Tagged protein localization | Visualizing cold-responsive proteins |
| CRISPR overexpression | Gain-of-function phenotypes | Enhancing cold tolerance |
Transcriptomics (RNA-seq)
RNA sequencing is widely used to profile gene expression changes during cold stress. In Min pig skeletal muscle, RNA-seq revealed cold-responsive genes and pathways. In plants, transcriptomics has identified CBF regulons and cold-regulated genes.
Proteomics and metabolomics
Proteomic and metabolomic approaches complement transcriptomics by measuring protein abundance and metabolite levels. Cold acclimation in plants involves accumulation of cryoprotectants and protective proteins, which can be quantified by these methods.
Behavioral assays
Behavioral assays in zebrafish have been used to quantify social behavior changes under acute cold stress. In humans, epidemiological and psychological studies assess cold susceptibility and social factors.
Genetic and CRISPR screens
CRISPR-based knockout, point mutation, knock-in, and overexpression models enable causal testing of genes annotated to GO:0009409. Such models can be used in plants, pigs, and zebrafish to dissect cold response mechanisms.
How CRISPR Can Be Used to Study GO:0009409 response to cold
Knockout
CRISPR knockout is used to delete cold-responsive genes to assess their necessity in the response to cold. For example, knocking out CBF genes in Arabidopsis reduces freezing tolerance. In pigs, knockout of HSP70 in skeletal muscle cells can test its role in cold stress survival.
Point Mutation
Point mutations introduced by CRISPR base editing or homology-directed repair can dissect specific amino acid residues in cold signaling proteins. For instance, mutating phosphorylation sites in ICE1 can reveal their role in cold-responsive transcription.
Knock-in
Knock-in of tags or reporters allows visualization and biochemical analysis of cold-responsive proteins. Tagged CBF1 knock-in in plants can reveal its dynamic localization during cold exposure.
Overexpression
CRISPR activation or transgenic overexpression can test gain-of-function effects. Overexpression of COR15A or CBF1 in plants enhances freezing tolerance, demonstrating sufficiency.
How EDITGENE Supports response to cold Research
Researchers studying response to cold-related genes often need to determine whether a candidate gene is causally involved in cold adaptation or merely correlated with cold-induced expression changes. CRISPR-based models provide the gold standard for establishing causality, and EDITGENE offers a comprehensive suite of services to generate such models efficiently.
Contact EDITGENE today to design your custom CRISPR model for response to cold research.
Frequently Asked Questions About response to cold
What is GO:0009409 response to cold?
GO:0009409 response to cold is a biological process term defined as any process that results in a change in state or activity of a cell or an organism as a result of a cold stimulus, a temperature below the optimal temperature for that organism.
What genes are involved in response to cold?
Genes involved in response to cold include CBF/DREB1 transcription factors, ICE1, COR15A, HSP70, SOD, and many others across plants and animals.
How is response to cold studied?
Response to cold is studied using RNA-seq, proteomics, metabolomics, behavioral assays, and CRISPR-based genetic models.
What is the synonym for GO:0009409?
The synonym for GO:0009409 is freezing tolerance.
Why is response to cold important in plants?
In plants, response to cold is critical for freezing tolerance and crop yield, and it overlaps with drought signaling networks.
How does cold stress affect pigs?
Cold stress in pigs alters skeletal muscle gene expression and metabolic pathways, which can impact meat quality and animal health.
Does cold cause the common cold?
The common cold is caused by viruses, but psychological stress and social factors can modulate susceptibility, and cold exposure may influence immune function.
What are CRISPR models for response to cold?
CRISPR models include knockout, point mutation, knock-in, and overexpression cell lines that enable causal testing of cold-responsive genes.
How does zebrafish respond to cold stress?
Zebrafish under acute cold stress show altered social behaviors, providing a model for neurobehavioral cold adaptation.
What services does EDITGENE offer for cold response research?
EDITGENE offers CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services for cold response gene studies.
Conclusion
GO:0009409 response to cold is a fundamental biological process that spans plants, animals, and humans, with implications for agriculture, metabolism, neurobehavior, and disease susceptibility. Understanding its molecular mechanisms requires integrated approaches, including transcriptomics, proteomics, and CRISPR-based functional genomics. As climate variability increases, research into cold response will remain essential for crop resilience, livestock management, and human health.
References
- 1. Zhang D et al.. 2022. Min pig skeletal muscle response to cold stress.. PLoS One 17(9):e0274184 PMID: 36155652
- 2. Kim JS et al.. 2024. Regulatory networks in plant responses to drought and cold stress.. Plant Physiol 195(1):170-189 PMID: 38514098
- 3. Cohen S et al.. 1997. Social ties and susceptibility to the common cold.. JAMA 277(24):1940-4 PMID: 9200634
- 4. Cohen S et al.. 1991. Psychological stress and susceptibility to the common cold.. N Engl J Med 325(9):606-12 PMID: 1713648
- 8. Liu ST et al.. 2024. Alternation of social behaviors for zebrafish (Danio rerio) in response to acute cold stress.. Fish Physiol Biochem 50(2):653-666 PMID: 38214794
