We have recently developed a prototype system for long-term monitoring of single-cell behaviors in complex tissues. Our system comes from the synergistic integration and optimization of two leading technologies in microscopy and computational cell tracking: the inverted selective plane illumination microscope (iSPIM) and the StarryNite software package. We have demonstrated order-of-magnitude improvements on virtually all fronts compared to the standard technologies in use, notably imaging speed, reduction of phototoxicity, accuracy of cell tracking, and lower demand for computing power, all achieved at a reduced cost with comparable or better image quality. Our system has been applied to multiple model organisms as well as cell culture, demonstrating its versatility.
We aim to bring the system to maturity and into the hands of the research community as a powerful and versatile tool for single-cell studies in complex, differentiating cell populations.

Public Health Relevance

Long-term monitoring of single cells in the context of complex tissues is crucial for the understanding of cell biological changes in physiological contexts and disease. Here we propose to develop a mature system to monitor individual cells in complex tissues based on a novel microscopy and computer-based automated image analysis system. Our system will provide a powerful tool to enable the research community to achieve better understanding on a wide range of health relative questions at unprecedented temporal and spatial resolution, from birth defects to brain function and viral infection.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-CB-D (50))
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Mukhopadhyay, Mahua
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Sloan-Kettering Institute for Cancer Research
New York
United States
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Santella, Anthony; Kovacevic, Ismar; Herndon, Laura A et al. (2016) Digital development: a database of cell lineage differentiation in C. elegans with lineage phenotypes, cell-specific gene functions and a multiscale model. Nucleic Acids Res 44:D781-5
Roy, Debasmita; Michaelson, David; Hochman, Tsivia et al. (2016) Cell cycle features of C. elegans germline stem/progenitor cells vary temporally and spatially. Dev Biol 409:261-71
Du, Zhuo; Santella, Anthony; He, Fei et al. (2015) The Regulatory Landscape of Lineage Differentiation in a Metazoan Embryo. Dev Cell 34:592-607
Santella, Anthony; Du, Zhuo; Bao, Zhirong (2014) A semi-local neighborhood-based framework for probabilistic cell lineage tracing. BMC Bioinformatics 15:217
Wu, Yicong; Wawrzusin, Peter; Senseney, Justin et al. (2013) Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy. Nat Biotechnol 31:1032-8
Moore, Julia L; Du, Zhuo; Bao, Zhirong (2013) Systematic quantification of developmental phenotypes at single-cell resolution during embryogenesis. Development 140:3266-74