Origins of cardiac fibroblasts - PubMed (original) (raw)

Figure 1. Fate mapping

A, Schematic displaying the principles of fate mapping using the example of EndMT. Basic principle of fate mapping is that specific cells (in this example, endothelial cells) are irreversibly labeled, in most cases, using dyes, DNA vectors, or transgenic reporters. If a labeled cell migrates from its original site, it will take its tag with it (in this example, the blue fibroblast leaving the endothelium). Because the label stays intact, tissue analysis at later time points allows for reconstruction of cellular ancestries, independent of their present phenotype or location (in this example, the blue label allows for identification of their endothelial origin of select fibroblasts). B, Picture summarizing the Cre/lox system, which is often used for fate mapping in mice using Tie1-Cre;R26-STOP-LacZ double-transgenic mice as example. In these mice, the Cre-recombinase is expressed under the endothelial cell–specific promoter Tie1 (top transgene schematic). R26R-STOP-lacZ mice carry a reporter transgene (in this case, LacZ, which encodes for bacterial _β_-galactosidase, allowing for distinction from mouse cells), which is controlled by a ubiquitous promoter that is active in most cell types (in this case, the R26 Rosa promoter). Because a STOP cassette (flanked by 2 loxP sites) is inserted between promoter and LacZ gene, the reporter gene is inactive (middle transgene schematic). When Tie-Cre mice are crossed to R26R-STOP-lacZ mice, Cre-recombinase (under control of endothelial cell–specific Tie1 promoter) removes the STOP cassette selectively in endothelial cells. The ubiquitous R26 promoter now constitutively drives LacZ expression, irrespective of the later fate of the endothelial cells, allowing for identification of endothelial origin.