Single-cell transcriptomics of human-skin-equivalent organoids.

Autor:	Stabell AR; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA., Lee GE; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Jia Y; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Wong KN; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA., Wang S; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA., Ling J; Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA., Nguyen SD; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Sen GL; Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA., Nie Q; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA., Atwood SX; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: satwood@uci.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 May 30; Vol. 42 (5), pp. 112511. Date of Electronic Publication: 2023 May 16.
DOI:	10.1016/j.celrep.2023.112511
Abstrakt:	Several methods for generating human-skin-equivalent (HSE) organoid cultures are in use to study skin biology; however, few studies thoroughly characterize these systems. To fill this gap, we use single-cell transcriptomics to compare in vitro HSEs, xenograft HSEs, and in vivo epidermis. By combining differential gene expression, pseudotime analyses, and spatial localization, we reconstruct HSE keratinocyte differentiation trajectories that recapitulate known in vivo epidermal differentiation pathways and show that HSEs contain major in vivo cellular states. However, HSEs also develop unique keratinocyte states, an expanded basal stem cell program, and disrupted terminal differentiation. Cell-cell communication modeling shows aberrant epithelial-to-mesenchymal transition (EMT)-associated signaling pathways that alter upon epidermal growth factor (EGF) supplementation. Last, xenograft HSEs at early time points post transplantation significantly rescue many in vitro deficits while undergoing a hypoxic response that drives an alternative differentiation lineage. This study highlights the strengths and limitations of organoid cultures and identifies areas for potential innovation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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