期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 37, 期 -, 页码 35-43出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2014.09.015
关键词
Cell signaling; Single-cell analysis; Computational modeling; Time-lapse microscopy
资金
- National Institutes of Health [R00-GM102372, R00-GM102372-S]
Signaling proteins are flexible in both form and function. They can bind to multiple molecular partners and integrate diverse types of cellular information. When imaged by time-lapse microscopy, many signaling proteins show complex patterns of activity or localization that vary from cell to cell. This heterogeneity is so prevalent that it has spurred the development of new computational strategies to analyze single-cell signaling patterns. A collective observation from these analyses is that cells appear less heterogeneous when their responses are normalized to, or synchronized with, other single-cell measurements. In many cases, these transformed signaling patterns show distinct dynamical trends that correspond with predictable phenotypic outcomes. When signaling mechanisms are unclear, computational models can suggest putative molecular interactions that are experimentally testable. Thus, computational analysis of single-cell signaling has not only provided new ways to quantify the responses of individual cells, but has helped resolve longstanding questions surrounding many well-studied human signaling proteins including NF-kappa B, p53, ERK1/2, and CDK2. A number of specific challenges lie ahead for single-cell analysis such as quantifying the contribution of non-cell autonomous signaling as well as the characterization of protein signaling dynamics in vivo. (C) 2014 Elsevier Ltd. All rights reserved.
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