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

Cell Reports (Mar 2020)

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

Affiliations

Daniel Haensel: 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
Suoqin Jin: Department of Mathematics, University of California, Irvine, CA 92697, USA
Peng Sun: Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA
Rachel Cinco: Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA
Morgan Dragan: 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
Quy Nguyen: Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA
Zixuan Cang: 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
Yanwen Gong: 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
Remy Vu: 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
Adam L. MacLean: Department of Mathematics, University of California, Irvine, CA 92697, USA
Kai Kessenbrock: Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA
Enrico Gratton: Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA
Qing Nie: 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; Corresponding author
Xing Dai: 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; Corresponding author

Journal volume & issue: Vol. 30, no. 11
pp. 3932 – 3947.e6

Abstract

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Summary: 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 Col17a1Hi/Trp63Hi 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. : Haensel et al. performed a comprehensive dissection of the cellular makeup of skin during homeostasis and wound healing and the molecular heterogeneity and cellular dynamics within its stem-cell-containing epidermal basal layer. Their work provides insights and stimulates further investigation into the mechanism of skin maintenance and repair. Keywords: single-cell RNA sequencing, skin, stem cell, epidermis, wound healing, metabolism, basal cell state, cellular transition dynamics, FLIM, plasticity

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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