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(Seminar) Reconstruct cellular dynamics from single cell data
08/06
2020
- Title (Seminar) Reconstruct cellular dynamics from single cell data
- Speaker
- Date
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Abstract
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CAS Key Laboratory of Theoretical Physics | |||
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Institute of Theoretical Physics | |||
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Chinese Academy of Sciences | |||
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Seminar | |||
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Title 题目 |
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Speaker 报告人 |
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Affiliation 所在单位 |
美国匹兹堡大学医学院 | ||
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Date 日期 |
2020年8月6日（星期四）10:30 - 11:30 | ||
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Venue 地点 |
ITP South Building 6620 | ||
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Contact Person 所内联系人 |
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Abstract 摘要 |
Recent advances of single cell techniques catalyzed quantitative studies on the dynamics of cell phenotypic transitions (CPT) emerging as a new field. Two grand technical challenges, however, impede further development of the field. Fixed cell-based approaches can provide snapshots of high-dimensional expression profiles but have fundamental limits on revealing temporal information, and fluorescence-based live cell imaging approaches provide temporal information but are technically challenging for multiplex long- term imaging. To tackle the challenges we developed an integrated experimental/computational platform for reconstructing single cell phenotypic transition dynamics. We first developed a live-cell imaging platform that tracks cellular status change through combining endogenous fluorescent labeling that minimizes perturbation to cell physiology, and/or live cell imaging of high-dimensional cell morphological and texture features. With our platform and an A549 VIM-RFP EMT reporter cell line, recorded live cell trajectories reveal parallel paths of epithelial-to-mesenchymal transition missing from snapshot data due to cell-cell dynamic heterogeneity. Recognizing that CPTs are examples of rate processes, we introduced transition path analyses and the concept of reaction coordinate from the well-established rate theories into CPT studies, and applied on this EMT process. We modified a finite temperature string method to reconstruct the reaction coordinate from the trajectories, and reconstruct a corresponding quasi-potential. The potential reveals that the EMT process under study resembles a barrier-less relaxation process. Thus our work demonstrates the necessity of extracting dynamical information of phenotypic transitions and the existence of a unified theoretical framework describing transition and relaxation dynamics in systems with and without detailed balance. | ||