Tracing development and disease
Lineage tracing, a means of tracking of cells during development and disease progression to obtain with high spatiotemporal resolution information on cell behavior, requires a high contrast view of the tissue with easily segmentable (i.e., separatable and trackable) features.
Most techniques for lineage tracing can be split into two general categories, (1) sparse/partial and (2) global cell labeling and tracking. Sparse cell labeling methodologies include traditional lineage tracing attempts, including dye labeling and tracking and random sparse cell labeling. Although this approach simplifies the problem of tracking cells in time and space by focusing solely on cells of interest, cell tracing data lacks contextual information about unlabeled cell behaviors within the surrounding tissue environment. Global lineage tracing requires labeling of all cells, usually with ubiquitous nuclear fluorescent protein expression, followed by sophisticated feature extraction and tracking using complex computer algorithms.
To combine the advantages of global and sparse/partial cell labeling into a single transgenic tool, we developed transgenic zebrafish lines called PhOTO (photoconvertible optical tracking of development and regeneration) zebrafish. We have demonstrated that these tools are ideal for the study of early developmental patterning as well as late-stage adult tissue regeneration.
However, it remains still quite challenge to track single cells and trace their corresponding lineages simultaneously in a complex environment. To circumvent this restriction, we are currently developing a novel lineage tracing tool - PhOTO-Bow - that realizes both targeted single-cell tracking and long-term lineage tracing by taking advantage of the recently developed primed conversion toolkit. PhOTO-Bow will provide a powerful resource to study cellular dynamic during disease progression and development.