Lineage Tracing Evidence of Pericyte Transdifferentiation into a Pathogenic Fibroblast Subpopulation after Myocardial Infarction
GU Qianyu, CHEN Haiting, XIE Jun*
This study aims to investigate whether pericytes can transdifferentiate into the pathogenic fibroblast subset F-Act after MI (myocardial infarction) and to elucidate their role in adverse ventricular remodeling using a double transgenic lineage tracing system. Cspg4CreERT2/+ knock-in mice were generated using CRISPR/Cas9 technology and crossed with Rosa26loxP-tdTomato-loxP-GFP/+ reporter mice to establish a tamoxifen-inducible pericyte lineage tracing model. Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery. Heart tissues were collected before MI and at 7, 14, and 28 days post-MI. Multicolor immunofluorescence staining was performed using CD248 as a specific marker for the late-activated fibroblast subset F-Act, and the phenotypic characteristics of pericyte-derived cells were observed by confocal microscopy. Genotyping and immunofluorescence validation confirmed that the model achieved efficient and specific lineage labeling of cardiac pericytes. Following MI, a time-dependent increase in GFP+ cells were observed in the infarct border zone, with a substantial proportion of GFP+ cells exhibiting clear co-localization with CD248+ cells, demonstrating that pericyte-derived cells express the characteristic marker of the F-Act subset. This study demonstrates that during the maturation phase of myocardial infarction repair, pericytes can transdifferentiate into the pathogenic fibroblast subset F-Act. This process may contribute to adverse ventricular remodeling and chronic fibrosis progression, providing a novel cellular source for understanding the mechanisms underlying post-MI fibrosis.
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