{"doi":"10.7554/elife.74866","title":"Epithelial-to-mesenchymal transition proceeds through directional destabilization of multidimensional attractor","abstract":"How a cell changes from one stable phenotype to another one is a fundamental problem in developmental and cell biology. Mathematically, a stable phenotype corresponds to a stable attractor in a generally multi-dimensional state space, which needs to be destabilized so the cell relaxes to a new attractor. Two basic mechanisms for destabilizing a stable fixed point, pitchfork and saddle-node bifurcations, have been extensively studied theoretically; however, direct experimental investigation at the single-cell level remains scarce. Here, we performed live cell imaging studies and analyses in the framework of dynamical systems theories on epithelial-to-mesenchymal transition (EMT). While some mechanistic details remain controversial, EMT is a cell phenotypic transition (CPT) process central to development and pathology. Through time-lapse imaging we recorded single cell trajectories of human A549/Vim-RFP cells undergoing EMT induced by different concentrations of exogenous TGF-β in a multi-dimensional cell feature space. The trajectories clustered into two distinct groups, indicating that the transition dynamics proceeds through parallel paths. We then reconstructed the reaction coordinates and the corresponding quasi-potentials from the trajectories. The potentials revealed a plausible mechanism for the emergence of the two paths where the original stable epithelial attractor collides with two saddle points sequentially with increased TGF-β concentration, and relaxes to a new one. Functionally, the directional saddle-node bifurcation ensures a CPT proceeds towards a specific cell type, as a mechanistic realization of the canalization idea proposed by Waddington.","journal":"eLife","year":2022,"id":246049,"datarank":1.2997441342892886,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.7254479248159243,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.7254479248159243,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":38,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.7h44j0zvp"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":881754,"name":"Dante Poe","orcid":"0000-0002-4813-3035","position":1,"is_corresponding":false},{"id":881755,"name":"Yaxuan Yang","orcid":"0000-0003-3077-2813","position":2,"is_corresponding":false},{"id":881756,"name":"Thomas Hyatt","orcid":"0000-0001-7536-0850","position":3,"is_corresponding":false},{"id":279287,"name":"Jianhua Xing","orcid":"0000-0002-3700-8765","position":4,"is_corresponding":false},{"id":279281,"name":"Weikang Wang","orcid":"0000-0002-4783-7540","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35188459","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}