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Single-cell RNA-sequencing of skin immune cells uncover a role for Angptl4-mediated ifi20b expression in monocyte cell fate differentiation during wound healing

ABSTRACT: Angiopoietin-like protein 4 (Angptl4) is a matricellular protein that associates with extracellular matrix proteins, mediating complex cell-cell, and cell-matrix interactions. It has been implicated in various inflammation-associated diseases, including wound healing, but very few reports describe a direct role for Angptl4 in the immune landscape of wound microenvironment. Here, we studied whether Angptl4 regulates the immune response during wound healing. Using single-cell RNA sequencing to examine the temporal changes in the immune cell landscape of excisional wounds from wild type and Angplt4-knockout (Angplt4-/-) mice revealed that Angptl4-/- wounds had a stalled inflammatory phase. Infiltrated neutrophils remained elevated in the Angptl4-/- wounds due to an impaired monocyte to macrophage differentiation needed for clearance. The impaired monocyte differentiation was also validated in wounds using multi-color flow cytometry. Pairwise comparisons of differentially expressed genes from wound-derived and bone-marrow derived macrophages demonstrated few differences, suggesting that Angptl4 has a confined regulome. We identified interferon activated protein 202B (ifi202b) to be consistently upregulated in Angptl4-/- macrophages. . Pathway analysis further confirmed that ifi202b significantly impacted multiple gene networks involved in the cell fate of monocytes and the functions of monocyte-derived macrophages. Taken altogether, we conclude that Angptl4 orchestrates the inflammatory state, innate immune landscape, and healing process in the wound microenvironment via its transcriptional regulation on ifi202b.

ORGANISM(S): Mus musculus

PROVIDER: GSE186986 | GEO | 2022/03/02

REPOSITORIES: GEO

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