Tissue-resident macrophages specifically express Lactotransferrin and Vegfc during ear pinna regeneration in spiny mice

Dev Cell. 2024 Jan 10:S1534-5807(23)00697-4. doi: 10.1016/j.devcel.2023.12.017. Online ahead of print.ABSTRACTThe details of how macrophages control different healing trajectories (regeneration vs. scar formation) remain poorly defined. Spiny mice (Acomys spp.) can regenerate external ear pinnae tissue, whereas lab mice (Mus musculus) form scar tissue in response to an identical injury. Here, we used this dual species system to dissect macrophage phenotypes between healing modes. We identified secreted factors from activated Acomys macrophages that induce a pro-regenerative phenotype in fibroblasts from both species. Transcriptional profiling of Acomys macrophages and subsequent in vitro tests identified VEGFC, PDGFA, and Lactotransferrin (LTF) as potential pro-regenerative modulators. Examining macrophages in vivo, we found that Acomys-resident macrophages secreted VEGFC and LTF, whereas Mus macrophages do not. Lastly, we demonstrate the requirement for VEGFC during regeneration and find that interrupting lymphangiogenesis delays blastema and new tissue formation. Together, our results demonstrate that cell-autonomous mechanisms govern how macrophages react to the same stimuli to differentially produce factors that facilitate regeneration.PMID:38228141 | DOI:10.1016/j.devcel.2023.12.017

Source: Developmental Cell - January 16, 2024 Category: Cytology Authors: Jennifer Simkin Ajoy Aloysius Mike Adam Fatemeh Safaee Ren ée R Donahue Shishir Biswas Zohaib Lakhani John C Gensel David Thybert Steven Potter Ashley W Seifert Source Type: research