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

Jennifer Simkin, Ajoy Aloysius, Mike Adam, Fatemeh Safaee, Renée R. Donahue, Shishir Biswas, Zohaib Lakhani, John C. Gensel, David Thybert, Steven Potter, Ashley W. Seifert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The 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.

Original languageEnglish
Pages (from-to)496-516.e6
JournalDevelopmental Cell
Volume59
Issue number4
DOIs
StatePublished - Feb 26 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Inc.

Keywords

  • Csf1r
  • Lactotransferrin
  • Vegfc
  • lymphangiogenesis
  • macrophage
  • regeneration
  • resident macrophage
  • spiny mouse
  • wound healing

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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