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A multi-step completion process model of cell plasticity.

作者信息

Chen Chen M, Yu Rosemary

机构信息

Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Faculty of Science, Radboud University, Geert Grooteplein-Zuid 26-28, Nijmegen, 6525GA, The Netherlands.

出版信息

Brief Bioinform. 2025 Mar 4;26(2). doi: 10.1093/bib/bbaf165.


DOI:10.1093/bib/bbaf165
PMID:40223810
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11995008/
Abstract

Plasticity is the potential for cells or cell populations to change their phenotypes and behaviors in response to internal or external cues. Plasticity is fundamental to many complex biological processes, yet to date there remains a lack of mathematical models that can elucidate and predict molecular behaviors in a plasticity program. Here, we report a new mathematical framework that models cell plasticity as a multi-step completion process, where the system moves from the initial state along a path guided by multiple intermediate attractors until the final state (i.e. a new homeostasis) is reached. Using omics time-series data as model input, we show that our method fits data well; identifies attractor states by their timing and molecular markers which are well-aligned with domain knowledge; and can make quantitative and time-resolved predictions such as the molecular outcomes of blocking a plasticity program from reaching completion, to an R2 of 0.53-0.63. We demonstrate that application of our model to primary patient-derived data can provide quantitative insights and predictions that may be useful in guiding further research and potential biomedical interventions.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/057dcf3a1002/bbaf165f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/9b9d977bc211/bbaf165f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/7b02df9133b2/bbaf165f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/181c56d71e5b/bbaf165f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/057dcf3a1002/bbaf165f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/9b9d977bc211/bbaf165f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/7b02df9133b2/bbaf165f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/181c56d71e5b/bbaf165f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ae8/11995008/057dcf3a1002/bbaf165f4.jpg

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本文引用的文献

[1]
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Mol Cell. 2024-6-6

[2]
Cellular plasticity in reprogramming, rejuvenation and tumorigenesis: a pioneer TF perspective.

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[3]
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[4]
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PLoS Genet. 2022-5-10

[5]
FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer.

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[6]
DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update).

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[7]
Novel insights from a multiomics dissection of the Hayflick limit.

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[8]
TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data.

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[9]
Inferring phenomenological models of first passage processes.

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[10]
Human epidermal stem cell differentiation is modulated by specific lipid subspecies.

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