Cooperative Interactions Research Articles

Colossal magnetoresistance from spin-polarized polarons in an Ising system

Recent experiments suggest a new paradigm toward novel colossal magnetoresistance (CMR) in a family of materials EuM 2 X 2 (M = Cd, In, Zn; X = P, As), distinct from the traditional avenues involving Kondo–Ruderman–Kittel–Kasuya–Yosida crossovers, magnetic phase transitions with structural distortions, or topological phase transitions. Here, we use angle-resolved photoemission spectroscopy and density functional theory calculations to explore their origin, particularly focusing on EuCd 2 P 2 . While the low-energy spectral weight royally tracks that of the resistivity anomaly near the temperature with maximum magnetoresistance ( T MR ) as expected from transport-spectroscopy correspondence, the spectra are completely incoherent and strongly suppressed with no hint of a Landau quasiparticle. Using systematic material and temperature dependence investigation complemented by theory, we attribute this nonquasiparticle caricature to the strong presence of entangled magnetic and lattice interactions, a characteristic enabled by the p - f mixing. Given the known presence of ferromagnetic clusters, this naturally points to the origin of CMR being the scattering of spin-polarized polarons at the boundaries of ferromagnetic clusters. These results are not only illuminating to investigate the strong correlations and topology in EuCd 2 X 2 family, but, in a broader view, exemplify how multiple cooperative interactions can give rise to extraordinary behaviors in condensed matter systems.

Unlocking AI Creativity: A Multi-Agent Approach with CrewAI

By automating processes that traditionally require human intelligence, such as learning, reasoning, and problem-solving, Artificial Intelligence (AI) has transformed many industries. Even with these developments, System 1 thinking is quick, providing instinctive reactions, while System 2 thinking entails thorough analysis and reasoned decision-making. AI systems still have a long way to go before they can replicate System 2 thinking—deliberate, analytical, and essential for managing complex problems. This study investigates how Multi-Agent Systems (MAS) integrate System 2 thinking into AI, concentrating on CrewAI, a no-code framework designed to improve AI creativity and decision-making. Unlike TensorFlow Agents and OpenAI’s Gym, which are limited to single-agent reinforcement learning, CrewAI excels in handling multi-agent, real-world tasks through collaboration. This study explores practical applications of CrewAI, such as intelligent grid management, automated customer support, and advertising. These examples highlight how CrewAI promotes AI creativity and problem-solving through cooperative agent interactions, leveraging System 2 thinking. Problems like scalability and coordination are also addressed, with solutions such as dynamic role assignment and hierarchical task management. In summary, the integration of System 2 thinking into MAS frameworks like CrewAI signifies progress toward creating intelligent, dependable AI systems capable of tackling the complexities of real-world problems.

Insights into the cooperative interaction of cage-type graphene-based Fe, Mo dual atom catalysts in nitrogen reduction reaction

Insights into the cooperative interaction of cage-type graphene-based Fe, Mo dual atom catalysts in nitrogen reduction reaction

Allelic variation in the promoter of WRKY22 enhances humid adaptation of Arabidopsis thaliana

Submergence tolerance is a complex trait governed by multiple genetic loci. Arabidopsis thaliana, widely distributed from arid to humid regions, offers an opportunity to explore the underlying genetic components and their interactive mechanisms. In this study, we utilized map-based cloning techniques to identify the WRKY22 genetic locus, which activates RAP2.12, a locus identified previously, possibly through ethylene signal transduction. WRKY22 expression is inhibited by ARRs but activated by the WRKY70 transcription factors. The cooperative interaction between these regulators enhances A. thaliana’s ability to adapt more effectively to contrasting habitats. A two-nucleotide deletion in the WRKY22 promoter region prevents its inhibition by phosphorylated ARRs, maintaining its high expression in humid accessions. This WRKY22 allele without ARRs binding element underwent strong natural selection during the southeastern colonization of A. thaliana to the humid Yangtze River basin. However, the WRKY70-activated WT box in the WRKY22 promoter region shows no variation between humid and arid accessions. These findings together establish one previously unreported molecular module composed by multiple regulators, with WRKY22 playing a key role in the ecological shift of A. thaliana. Expanding upon the identified locus, we overexpressed BnaC2.WRKY22 in Brassica napus and successfully achieved a significant improvement in submergence tolerance, highlighting a functional conservatism of this gene across related species. This further demonstrates the potential for transferring knowledge from model plants to crops for the breeding of flood-tolerant crop varieties.

An oncoprotein CREPT functions as a co-factor in MYC-driven transformation and tumor growth

Understanding the mechanisms behind MYC-driven oncogenic transformation could pave the way for identifying novel drug targets. This study explored the role of CREPT in MYC-induced malignancy by generating MYC-transformed mouse embryonic fibroblasts (MEFs) with conditional CREPT deletion. Our results demonstrated that the loss of CREPT significantly impaired MYC-induced colony formation and cell proliferation, indicating that CREPT is essential for the malignant transformation of MEFs. Reintroducing CREPT in CREPT-deficient cells restored malignant properties. Furthermore, CREPT overexpression alone enhanced colony formation upon MYC induction but was insufficient to induce transformation without MYC, suggesting a cooperative interaction between CREPT and MYC in malignant transformation. CREPT deletion resulted in delayed cell cycle progression during the G2/M and S phases. CREPT enhanced the expression of MYC target genes by directly interacting with MYC through the CID domain of CREPT and the PEST domain of MYC. Arginine 34 of CREPT was identified as a critical residue for the interaction with MYC, and its mutation lost the ability of CREPT to promote MYC-driven colony formation and tumor growth in colorectal cancer models. Additionally, CREPT facilitated the recruitment of RNA Polymerase II (RNAPII) to MYC-binding promoters, promoting transcriptional initiation of MYC-targeted genes. Our study also revealed a strong correlation between CREPT and MYC expression in various human cancers, particularly in colorectal cancer, where their interaction appears to play a significant role in tumorigenesis. These findings suggest that the CREPT-MYC interaction is crucial for the progression of MYC-driven cancers and presents a potential target for therapeutic intervention.

Integrated impacts of mariculture on nitrogen cycling processes in the coastal groundwater of Beihai, southern China

Groundwater nitrogen (N) contamination in coastal zones is becoming an increasingly serious global issue. Mariculture, as a major anthropogenic activity, has profound impacts on coastal groundwater and constitutes an important source of coastal N contamination. However, a comprehensive understanding of the impact of mariculture on N cycling (especially N removal) is still lacking. Taking the Daguansha mariculture region in southern China as the study area, we aimed to investigate the environmental impact of mariculture on coastal groundwater and identify N cycling processes influenced by mariculture using hydrogeochemistry, multiple isotopes, coupled with 16S rRNA gene sequencing, and the quantitative polymerase chain reaction (qPCR) experiments. The results showed that the combined effects of seawater intrusion and seepage from land-based mariculture ponds have led to localized groundwater salinization in the region. Meanwhile, mariculture promotes nitrification and anammox processes in groundwater. The dominance of ammonia-oxidizing and anammox bacteria in the upper aquifer is attributable to local salinization, N and organic carbon input, as well as anoxic to suboxic conditions induced by seepage from aquaculture ponds. In addition, the gene abundances of ammonia oxidation (dominated by AOA) and denitrification were positively correlated, indicating their cooperative interaction. This study provides deeper insight into N cycling in coastal groundwater systems affected by extensive mariculture.

Hyperscanning speaks to the need to revise our understanding of the mind‒brain relation

Several research labs around the world have been developing and applying hyperscanning, an innovative methodology that allows to observe what happens in the brains of two or more people when they interact in different social/interpersonal settings. Hyperscanning findings seem to point to the fact that synchronized interbrain activity may be caused by cooperative social interaction, showing that traditionally dominant perspectives about the mind‒brain relation (in particular, supervenience and internalism regarding mental contents) should be revised or replaced by others that adequately integrate the influence of human interactions on the neurobiological underpinnings of cognition (e.g., contextual emergence, externalism regarding mental contents, 4E cognition). This shift would undeniably also have important implications in the fields of mental health (e.g., opening avenues for the design of diagnoses and treatments for social skill conditions) and the social sciences (regarding aspects such as sociocultural interplay, collective decision-making and public participation, social conflict and polarization, interpersonal curiosity, and autonomy).

Solvent-Directed Social Chiral Self-Sorting in Pd2L4 Coordination Cages.

A family of Pd2L4 cages prepared from ligands based on an axially chiral diamino-[1,1'-biazulene] motif (serving as a unique azulene-based surrogate of the ubiquitous BINOL moiety) is reported. We show that preparing a cage starting from the racemate of a shorter bis-monodentate ligand derivative, equipped with pyridine donor groups, leads to integrative ("social") chiral self-sorting, exclusively yielding the meso-trans product, but only in a selection of solvents. This phenomenon is driven by individual solvent molecules acting as hydrogen bonding tethers between the amino groups of neighboring ligands, thereby locking the final coordination cage in a single isomeric form. The experimental (solvent-dependent NMR, single-crystal X-ray diffraction) observations of this cooperative interaction could be explained by computational analyses only when explicit solvation was considered. Furthermore, we prepared a larger chiral ligand with isoquinoline donors, which, unlike the first one, does not undergo social self-sorting from its racemic mixture, further highlighting the importance of solvents bridging short distances between the amino groups. Homochiral cages formed from this larger ligand, however, furnish a cavity that can bind anionic and neutral metal complexes such as [Pt(CN)6]2- and Cr(CO)6 and discriminate between the two enantiomers of chiral guest camphor sulfonate.

Activation and Deactivation of Chirality Transfer in the Superbundles of Sequence-defined Stereoisomers.

Discrete oligomers can be used to precisely evaluate the structure-property relationship and enable unique chiroptical activities, however, the role of stereochemical sequences on chirality transfer is still unclear. Herein, we report the successful synthesis of a series of sequence-defined chiral azobenzene (Azo) oligomers via iterative stepwise chain growth strategy. Sequence-defined stereoisomers with one single chiral (L or D) stereocenter at the α-position, ω-position and middle- (m-) position have completely different self-assembly dynamics. ω-positional stereocenter can effectively command all Azo building blocks to adopt a tilted π-π stacking along the helical superbundles, exhibiting the activation of chirality transfer. However, discrete oligomers with the stereocenter at other positions can only self-assemble into non-helical nanowires, accompanied by the deactivation of chirality transfer.Cooperative supramolecular interactions, including the π-π interaction between Azo units, the intermolecular hydrogen bonding and steric hindrance, are intrinsic driving forces for these differentiations.

Activation and Deactivation of Chirality Transfer in the Superbundles of Sequence‐defined Stereoisomers

AbstractDiscrete oligomers can be used to precisely evaluate the structure–property relationship and enable unique chiroptical activities, however, the role of stereochemical sequences on chirality transfer is still unclear. Herein, we report the successful synthesis of a series of sequence‐defined chiral azobenzene (Azo) oligomers via iterative stepwise chain growth strategy. Sequence‐defined stereoisomers with one single chiral (L or D) stereocenter at the α‐position, ω‐position and middle‐ (m−) position have completely different self‐assembly dynamics. ω‐positional stereocenter can effectively command all Azo building blocks to adopt a tilted π–π stacking along the helical superbundles, exhibiting the activation of chirality transfer. However, discrete oligomers with the stereocenter at other positions can only self‐assemble into non‐helical nanowires, accompanied by the deactivation of chirality transfer.Cooperative supramolecular interactions, including the π–π interaction between Azo units, the intermolecular hydrogen bonding and steric hindrance, are intrinsic driving forces for these differentiations.

The Limits of Our Explanation: A Case Study in Myxococcus xanthus Cooperation

AbstractIn this article, I demonstrate two ways in which our major theories of the evolution of cooperation may fail to capture particular social phenomena. The first shortcoming of our current major theories stems from the possibility of mischaracterizing the cooperative problem in game theory. The second shortcoming of our current major theories is the insensitivity of these explanatory models to ecological and genomic context. As a case study to illustrate these points, I will use the cooperative interaction of a species of myxobacteria called Myxococcus xanthus. M. xanthus cooperate in many areas of their life cycle—in quorum sensing, social motility, fruiting body formation, and predation. I focus in particular on predation as we have not yet discovered an adequate explanation of how they sustain cooperative predation in the face of developmental cheats. In explaining why we have not, I draw generalizable conclusions that shed light on our use of simplified models to explain real-world behaviors in a variety of organisms.

Size and Surface Effects in the Ultrafast Dynamics of Strongly Cooperative Spin-Crossover Nanoparticles.

Cooperative photoinduced switching of molecular materials at the nanoscale is still in its infancy. Strongly cooperative spin-crossover nanomaterials are arguably the best prototypes of photomagnetic and volume-changing materials that can be manipulated by short pulses of light. Open questions remain regarding their non-equilibrium dynamics upon light excitation and the role of cooperative elastic interactions in nanoscale systems that are characterized by large surface/volume ratios. Femtosecond-resolved broadband spectroscopy is performed on nanorods of the strongly cooperative Fe-triazole, which undergoes a reversible low-spin to high-spin (HS) phase transition ≈360K. Supported by density functional theory and mechano-elastic Monte Carlo simulations, a marked difference is observed in the photoswitching dynamics at the surface of the nanoparticles compared with the core. Surprisingly, under low excitation (<2%) conditions, there occurs a transient increase in the HS population at the surface on the picosecond time scale, while the HS population in the core decays concomitantly. These results shed light onto the importance of surface properties and dynamical size limits of nanoscale photoresponsive nanomaterials that can be used in a broad range of applications.

Development of Oral, Potent, and Selective CK1α Degraders for AML Therapy.

Molecular glue degraders (MGDs) are proximity-inducing agents that mediate the cooperative interaction between a target protein and an E3 ligase, introducing an additional layer of specificity beyond that afforded by traditional small molecules. Historically, molecular glues that stabilize protein-protein interactions were often discovered serendipitously. In this study, we leveraged the reprogramming potential of cereblon (CRBN)-based ligands and conducted a CRBN-dependent proliferation screen to identify CRBN-based MGDs capable of inducing the degradation of proteins essential for cell viability. Through our screening and subsequent medicinal chemistry optimization, we identified dCK1α-1 as a potent and selective CK1α-targeting molecular glue degrader. Furthermore, we synthesized an orally active derivative, dCK1α-2, with enhanced pharmacokinetic properties, which exhibited pronounced degradation activity and demonstrated efficacy in mouse models following oral gavage. These findings indicate that phenotypic drug discovery campaigns, in combination with chemically distinct CRBN ligand libraries, can accelerate the development of therapeutically relevant MGDs. Furthermore, the development of dCK1α-1 and dCK1α-2 provides new therapeutic options for cancers with functional p53 signaling and offers valuable chemical tools for future investigations into the role of CK1α.

Effects of green innovation ecosystem coopetition, environmental management practices and digital innovation on carbon footprint reduction

Purpose The purpose of this article is to analysis of the effects of green innovation ecosystem coopetition (cooperation and competition), environmental management practices (EMPs) and digital innovation (DI) on carbon footprint reduction. Design/methodology/approach To conduct the study, a questionnaire was administered to hotel managers from different regions of Brazil. Data were collected from 197 hotels and analyzed via partial least squares structural equation modeling. Findings The results show that green innovation ecosystem cooperation positively and significantly affects EMPs and DI. Green innovation ecosystem competition interactions also benefit the adoption of EMPs. However, they do not significantly influence the use of DI. The results indicate that hotels that are in a scenario of simultaneous competition and collaboration (coopetition) within the green innovation ecosystem can reduce carbon emissions when EMPs and DI are used. Research limitations/implications The authors contribute to the literature by showing different pathways for reducing the carbon footprint of hotels. The results expand the authors’ knowledge by showing evidence that cooperation and competition interactions can produce distinct effects, especially on DI. Thus, this study has important practical implications for hotel managers seeking to improve their environmental practices and DI with the help of external multiagent resources and knowledge. Originality/value This research contributes to the literature by examining how cooperation and competition interactions in the green innovation ecosystem help in the adoption of environmental management and DI practices.

Impact of Bacillus Inoculation on Rhizosphere Bacterial Community Structure: A Review

The rhizosphere is a specialized zone where plant roots interact with the soil microbiome. Among various beneficial microbes, the genus Bacillus stands out due to its diverse functionalities and potential to boost plant growth and resilience. Bacillus is a key genus of plant growth-promoting rhizobacteria (PGPR) known for enhancing nutrient availability, producing phytohormones, and inducing plant resistance to pathogens. Inoculating Bacillus species into the rhizosphere can significantly alter the bacterial community's structure and composition. These alterations are driven by the competitive and cooperative interactions between Bacillus and the native rhizosphere microorganisms. Incorporating soil microorganisms into the host plant's beneficial bacterial community improves soil nutrient cycling and nutrient use efficiency. Using microbial inoculants is an effective strategy to address crop succession challenges, enhance microbial community structure, and improve soil fertility, thereby promoting crop growth. This review thoroughly examines the current understanding of how Bacillus inoculation impacts rhizosphere bacterial community structure.

Qihuang Zhuyu formula modulates mitochondrial function to inhibit platelet activation via endocannabinoid signaling mediated by the SIRT1/PPARα pathway

Ethnopharmacological relevanceDeveloping effective drugs is urgent for preventing platelet activation and atherosclerotic diseases. Qihuang Zhuyu formula (QHZYF) is a curative medical plants formula in clinic while its molecular mechanism remains to be further elucidated. Aim of the studyTo investigate how QHZYF, via the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor alpha (PPARα) pathway, mediates the endocannabinoid system, regulates mitochondrial function, and inhibits platelet activation, thereby offering novel strategies for the prevention and treatment of cardiovascular diseases. MethodsThe chemical constituents of QHZYF were characterized by ultra-performance liquid chromatography tandem with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). For the in vivo experiments, an atherosclerosis rat model was developed. Platelet activation and endocannabinoid levels were assessed by ELISA, while the expression of PPARα was evaluated by immunofluorescence. Additionally, the expression of endocannabinoid-degrading enzymes was analyzed by Western blotting. In the in vitro studies, the protein-protein interaction between SIRT1 and PPARα was initially investigated using co-immunoprecipitation (Co-IP). Thereafter, platelets were co-cultured with human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). The mitochondrial function of platelets was examined by flow cytometry. Platelet activation and endocannabinoid levels were quantified using ELISA, and the expression of PPARα, endocannabinoid-degrading enzymes and proteins reflecting mitochondrial function were determined by Western blotting. Subsequently, QHZYF was incorporated into the aforementioned system, and the entire experimental protocol was replicated to explore how QHZYF influences platelet activation through the SIRT1/PPARα pathway-mediated endocannabinoid system. ResultsIn the in vivo experiments, it was observed that QHZYF significantly augmented the levels of PPARα, concurrently with a decrease in the expression of endocannabinoid-degrading enzymes. This was paralleled by a rise in endogenous cannabinoid levels and a reduction in platelet activation, a process that was found to be regulated by SIRT1. The co-immunoprecipitation (Co-IP) analysis substantiated the cooperative interaction between SIRT1 and PPARα, underscoring their role in mediating the endocannabinoid system, regulating mitochondrial function, and consequently influencing platelet activation. In the in vitro studies, a co-culture system involving platelets and HUVECs stimulated with ox-LDL was employed. It was noted that the SIRT1/PPARα pathway mediates the endocannabinoid system in regulating mitochondrial function, which in turn affects platelet activation. The incorporation of QHZYF-containing serum into this system produced outcomes consistent with those observed in the in vivo experiments. These findings suggest that QHZYF operates by modulating the endocannabinoid system via the SIRT1/PPARα pathway, thereby controlling mitochondrial function and inhibiting platelet activation. ConclusionSIRT1 may mediate endocannabinoid signaling through its interaction with PPARα, regulating mitochondrial function and subsequently influencing platelet activation. QHZYF effectively modulates the endocannabinoid system via the SIRT1/PPARα pathway, thereby inhibiting platelet activation.

Behavioral inhibition and social maladjustment: The moderation role of social behaviors during cooperative and competitive peer interactions.

Behavioral inhibition (BI) is a temperamental characterized in early childhood by intense wariness and negative affect toward novelty, and is linked to children's emotional symptoms and peer problems. How children behave or respond toward diverse social contexts can influence the relation between BI and social adjustment. This study investigated the effect of children's affiliative and antagonistic behavior in cooperative and competitive contexts on the relation between early BI and social adjustment using a longitudinal design. Children's BI (at age 2) was assessed via laboratory observations. Affiliative and antagonistic behaviors (at age 4) were coded during a dyadic truck game in the cooperative and competitive contexts. Children's emotional symptoms and peer problems (at age 4) were assessed using parental reports. These results suggest that high affiliative behavior in the cooperative context was linked to a reduced level of peer problems in inhibited children. Interestingly, highly antagonistic behavior in the competitive context was linked to a reduced level of emotional symptoms in inhibited children. These findings extend our understanding of the role social behavior plays in the social adjustment of behaviorally inhibited children by highlighting the contribution of socially appropriate behaviors in social contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bioinspired Surface Engineering with Dual Covalent Receptors Incorporated via Precise Post-Imprinting Modification to Enhance the Specific Identification of Adenosine 5′-Monophosphate

Expanding the specific surface area of substrates and carrying out precise surface engineering of imprinted nanocavities are crucial methods for enhancing the identification efficiency of molecularly imprinted polymers (MIPs). To implement this synergistic strategy, bioinspired surface engineering was used to incorporate dual covalent receptors via precise post-imprinting modifications (PIMs) onto mesoporous silica nanosheets. The prepared sorbents (denoted as “D-PMIPs”) were utilized to improve the specific identification of adenosine 5′-monophosphate (AMP). Significantly, the mesoporous silica nanosheets possess a high surface area of approximately 498.73 m2∙g–1, which facilitates the formation of abundant specific recognition sites in the D-PMIPs. The dual covalent receptors are valuable for establishing the spatial orientation and arrangement of AMP through multiple cooperative interactions. PIMs enable precise site-specific functionalization within the imprinted cavities, leading to the tailor-made formation of complementary binding sites. The maximum number of high-affinity binding sites (Nmax) of the D-PMIPs is 39.99 μmol∙g–1, which is significantly higher than that of imprinted sorbents with a single receptor (i.e., S-BMIPs or S-PMIPs). The kinetic data of the D-PMIPs can be effectively described by a pseudo-second-order model, indicating that the main binding mechanism involves synergistic chemisorption from boronate affinity and the pyrimidine base. This study suggests that using dual covalent receptors and PIMs is a reliable approach for creating imprinted sorbents with high selectivity, allowing for the controlled engineering of imprinted sites.

Extraordinary piezoresponse in free-standing two-dimensional Bi2O2Se semiconductor toward high-performance light perception synapse

Localized strain engineering has a higher spatial modulation precision because it can generate noteworthy out-of-plane deformation, which shows novel physical properties for developing functional devices. However, the relevant research and the coupling with external fields has not been well developed. Here, we focus on disclosing the strain-optical-electrical cooperative interactions of the emerging two-dimensional (2D) Bi2O2Se semiconductor with a free-standing structure. The suspended Bi2O2Se exhibits remarkable out-of-plane electromechanical coupling. The piezoelectric coefficient of ∼ 13.1 pm/V from 8 nm nanoflake significantly surpasses that from its flat structure and the majority 2D materials. The generated back-to-back built-in electric field efficiently regulates transport carriers under optical stimulation, leading to a larger photogenerated current enhancement about 104 of a suspended Bi2O2Se device without gate voltage modulation. This device also displays an ultra-high-performance artificial synaptic function, which has thousands of changes in synaptic weight, superior paired-pulse facilitation, bio-similarity relaxation times, and an interesting “learning-experience” behavior similar to human beings. The realization of an electromechanical visualization model and excellent optoelectronic synaptic functions can promote the further development of 2D materials based flexoelectric applications.

Polyclonal-to-monoclonal transition in colorectal precancerous evolution.

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited1-3. Here we used a base editor-enabled DNA barcoding system4 to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent celllineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.