Lrat-Cre exhibe una expresión generalizada más allá de las células estrelladas hepáticas en múltiples tejidos

Hepatic stellate cells (HSCs) play a central role in liver fibrosis, shifting from quiescent vitamin A-storing cells to activated, myofibroblast-like cells that secrete collagen and other profibrotic factors ¹ . HSCs have thus become a major focus in liver fibrosis research, and several Cre driver lines have been created to target HSCs in mice. However, early Cre lines had significant limitations. Glial fibrillary acidic protein ( Gfap ) -Cre labels only a subset of HSCs and also induces recombination in cholangiocytes ² . Collagen type I alpha 1 ( Col1a1 ) -Cre and alpha-smooth muscle actin ( αSMA ) -Cre/CreERT2 primarily label activated myofibroblasts and broadly mark portal fibroblasts and vascular smooth muscle cells ^3,4 . Platelet-derived growth factor receptor beta ( Pdgfrβ ) -Cre reliably labels HSCs but also recombines pericytes and smooth muscle cells, limiting its specificity ⁵ . The introduction of lecithin-retinol acyltransferase ( Lrat ) -Cre marked a major advance, offering highly specific labeling of quiescent and activated HSCs and rapidly becoming the most widely used driver for HSC tracing and genetic perturbation ² . However, the extrahepatic expression of Lrat-Cre remains incompletely understood. This is a critical limitation, given that liver biology is closely coordinated with other organs to maintain systemic metabolism. Addressing these gaps is essential for the accurate interpretation of HSC-specific genetic models in liver biology.