Single-cell transcriptomics of human-skin-equivalent organoids
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723005223 |
| _version_ | 1797825597254139904 |
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| author | Adam R. Stabell Grace E. Lee Yunlong Jia Kirsten N. Wong Shuxiong Wang Ji Ling Sandrine D. Nguyen George L. Sen Qing Nie Scott X. Atwood |
| author_facet | Adam R. Stabell Grace E. Lee Yunlong Jia Kirsten N. Wong Shuxiong Wang Ji Ling Sandrine D. Nguyen George L. Sen Qing Nie Scott X. Atwood |
| author_sort | Adam R. Stabell |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-13T10:56:18Z |
| format | Article |
| id | doaj.art-663aeff6ac124671a4eb12468c589818 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T10:56:18Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-663aeff6ac124671a4eb12468c5898182023-05-17T04:22:43ZengElsevierCell Reports2211-12472023-05-01425112511Single-cell transcriptomics of human-skin-equivalent organoidsAdam R. Stabell0Grace E. Lee1Yunlong Jia2Kirsten N. Wong3Shuxiong Wang4Ji Ling5Sandrine D. Nguyen6George L. Sen7Qing Nie8Scott X. Atwood9Department 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, USADepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USADepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USADepartment 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, USADepartment of Mathematics, University of California, Irvine, Irvine, CA 92697, USADepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USADepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USADepartment 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, USADepartment 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, USADepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723005223CP: Stem cell research |
| spellingShingle | Adam R. Stabell Grace E. Lee Yunlong Jia Kirsten N. Wong Shuxiong Wang Ji Ling Sandrine D. Nguyen George L. Sen Qing Nie Scott X. Atwood Single-cell transcriptomics of human-skin-equivalent organoids Cell Reports CP: Stem cell research |
| title | Single-cell transcriptomics of human-skin-equivalent organoids |
| title_full | Single-cell transcriptomics of human-skin-equivalent organoids |
| title_fullStr | Single-cell transcriptomics of human-skin-equivalent organoids |
| title_full_unstemmed | Single-cell transcriptomics of human-skin-equivalent organoids |
| title_short | Single-cell transcriptomics of human-skin-equivalent organoids |
| title_sort | single cell transcriptomics of human skin equivalent organoids |
| topic | CP: Stem cell research |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723005223 |
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