Evidence map›Paper›PMID 35188459›Full record

ArticleeLife2022

Epithelial-to-mesenchymal transition proceeds through directional destabilization of multidimensional attractor.

Weikang Wang, Dante Poe, Yaxuan Yang, Thomas Hyatt, Jianhua Xing

Abstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Weikang WangDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0002-4783-7540
Dante PoeDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0002-4813-3035
Yaxuan YangDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0003-3077-2813
Thomas HyattDepartment of Physics and Astronomy, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0001-7536-0850
Jianhua XingDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0002-3700-8765

Funding

Integrated Interdisciplinary, inter-university PhD Program Computational Biology (T32)T32EB009403 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, BAR-JOSEPH, ZIV · 2009 to 2023
$4.4M
Three-dimensional organoid models to study breast cancer progressionR37CA232209 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SANT, SHILPA · 2018 to 2024
$3.0M
Role of the Snail1-Twist-p21 axis on cell cycle arrest and renal fibrosis developmentR01DK119232 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI XING, JIANHUA · 2019 to 2022
$1.4M
NCI NIH HHS R37 CA232209NIBIB NIH HHS T32 EB009403NIDDK NIH HHS R01 DK119232
6 · The paper itself

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.

Indexed as

Epithelial-Mesenchymal TransitionTransforming Growth Factor betaA549 CellsHumansTransforming Growth Factor betaA549 cell lineepithelial-to-mesenchymal transitionlive cell imagingnonephysics of living systemstransition path theory

Identifiers

PMID35188459
PMCPMC8920502

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.