Wound healing in aged skin exhibits systems-level alterations in cellular composition and cell-cell communication

Remy Vu; Suoqin Jin; Peng Sun; Daniel Haensel; Quy Hoa Nguyen; Morgan Dragan; Kai Kessenbrock; Qing Nie; Xing Dai

doi:10.1016/j.celrep.2022.111155

Wound healing in aged skin exhibits systems-level alterations in cellular composition and cell-cell communication

Cell Rep. 2022 Aug 2;40(5):111155. doi: 10.1016/j.celrep.2022.111155.

Authors

Remy Vu¹, Suoqin Jin², Peng Sun¹, Daniel Haensel¹, Quy Hoa Nguyen³, Morgan Dragan¹, Kai Kessenbrock³, Qing Nie⁴, Xing Dai⁵

Affiliations

¹ Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92627, USA.
² School of Mathematics and Statistics, Wuhan University, Wuhan 430072, China; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.
³ Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
⁴ The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92627, USA; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: qnie@uci.edu.
⁵ Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92627, USA. Electronic address: xdai@uci.edu.

Abstract

Delayed and often impaired wound healing in the elderly presents major medical and socioeconomic challenges. A comprehensive understanding of the cellular/molecular changes that shape complex cell-cell communications in aged skin wounds is lacking. Here, we use single-cell RNA sequencing to define the epithelial, fibroblast, immune cell types, and encompassing heterogeneities in young and aged skin during homeostasis and identify major changes in cell compositions, kinetics, and molecular profiles during wound healing. Our comparative study uncovers a more pronounced inflammatory phenotype in aged skin wounds, featuring neutrophil persistence and higher abundance of an inflammatory/glycolytic Arg1^Hi macrophage subset that is more likely to signal to fibroblasts via interleukin (IL)-1 than in young counterparts. We predict systems-level differences in the number, strength, route, and signaling mediators of putative cell-cell communications in young and aged skin wounds. Our study exposes numerous cellular/molecular targets for functional interrogation and provides a hypothesis-generating resource for future wound healing studies.

Keywords: CP: Cell biology; CP: Developmental biology; aging; cell-cell communication; cellular heterogeneity; dendritic cell; macrophage; neutrophil; signaling; single-cell RNA-seq; skin; wound healing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Communication
Fibroblasts* / metabolism
Macrophages / metabolism
Signal Transduction
Skin
Wound Healing*

Abstract

Publication types

MeSH terms

Grants and funding