Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

Daniel Haensel; Suoqin Jin; Peng Sun; Rachel Cinco; Morgan Dragan; Quy Nguyen; Zixuan Cang; Yanwen Gong; Remy Vu; Adam L MacLean; Kai Kessenbrock; Enrico Gratton; Qing Nie; Xing Dai

doi:10.1016/j.celrep.2020.02.091

Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

Cell Rep. 2020 Mar 17;30(11):3932-3947.e6. doi: 10.1016/j.celrep.2020.02.091.

Authors

Daniel Haensel¹, Suoqin Jin², Peng Sun³, Rachel Cinco⁴, Morgan Dragan¹, Quy Nguyen³, Zixuan Cang⁵, Yanwen Gong⁶, Remy Vu¹, Adam L MacLean², Kai Kessenbrock³, Enrico Gratton⁴, Qing Nie⁷, Xing Dai⁸

Affiliations

¹ Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA; The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92627, USA.
² Department of Mathematics, University of California, Irvine, CA 92697, USA.
³ Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA.
⁴ Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
⁵ The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92627, USA; Department of Mathematics, University of California, Irvine, CA 92697, USA.
⁶ Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, CA 92697, USA.
⁷ The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92627, USA; Department of Mathematics, University of California, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA. Electronic address: qnie@uci.edu.
⁸ Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA; The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92627, USA. Electronic address: xdai@uci.edu.

Abstract

Our knowledge of transcriptional heterogeneities in epithelial stem and progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem and progenitor potential, but a comprehensive dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses predict a quasi-linear differentiation hierarchy where basal cells progress from Col17a1^Hi/Trp63^Hi state to early-response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal transcriptional states. Our study provides a systematic view of epidermal cellular dynamics, supporting a revised "hierarchical-lineage" model of homeostasis.

Keywords: FLIM; basal cell state; cellular transition dynamics; epidermis; metabolism; plasticity; single-cell RNA sequencing; skin; stem cell; 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

Animals
Cell Movement / genetics
Epidermis / metabolism*
Epidermis / pathology*
Female
Gene Expression Profiling*
Homeostasis / genetics*
Inflammation / genetics
Inflammation / pathology
Mice, Inbred C57BL
Mice, Transgenic
Single-Cell Analysis*
Up-Regulation / genetics
Wound Healing / genetics*

Abstract

Publication types

MeSH terms

Grants and funding