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Published on: July 22, 2020
Attractor Landscape Analysis Reveals a Reversion Switch in the Transition of Colorectal Tumorigenesis
Dongkwan Shin1,2,3, Jeong-Ryeol Gong1, Seoyoon D Jeong1
1Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Abstract:
A cell fate change such as tumorigenesis incurs critical transition. It remains a longstanding challenge whether the underlying mechanism can be unraveled and a molecular switch that can reverse such transition is found. Here a systems framework, REVERT, is presented with which can reconstruct the core molecular regulatory network model and a reversion switch based on single-cell transcriptome data over the transition process is identified. The usefulness of REVERT is demonstrated by applying it to single-cell transcriptome of patient-derived matched organoids of colon cancer and normal colon. REVERT is a generic framework that can be applied to investigate various cell fate transition phenomena.
Insights
Researchers developed REVERT, a systems framework to identify molecular switches that reverse cell fate transitions like cancer. This method reconstructs regulatory networks from single-cell data, offering insights into diseases.
Area of Science:
- Systems biology
- Molecular biology
- Cancer research
Background:
- Cell fate transitions, such as tumorigenesis, represent critical biological changes.
- Understanding the mechanisms and identifying molecular switches to reverse these transitions remain significant challenges in biology and medicine.
Purpose of the Study:
- To present REVERT, a novel systems framework designed to reconstruct core molecular regulatory networks.
- To identify molecular switches capable of reversing cell fate transitions using single-cell transcriptome data.
Main Methods:
- Development of the REVERT systems framework.
- Application of REVERT to analyze single-cell transcriptome data from patient-derived matched organoids of colon cancer and normal colon.
Main Results:
- REVERT successfully reconstructed the core molecular regulatory network model.
- A molecular switch capable of reversing the cell fate transition was identified.
- The framework's utility was demonstrated in the context of colon cancer progression.
Conclusions:
- REVERT provides a powerful and generic framework for investigating cell fate transitions.
- The identified molecular switch offers potential therapeutic targets for reversing tumorigenesis.
- This approach can be broadly applied to various cell fate transition phenomena beyond cancer.
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