Single cell transcriptomics of human epidermis identifies basal stem cell transition states
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Abstract
How stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.
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scRNA-seq enables profiling of gene expression at single-cell resolution and identification of reliable cellular heterogeneity, allowing identification of previously unrecognized heterogeneity, revealing regulatory relationships between genes, and tracking trajectories of distinct cell lineages.
“It enables both profiling of gene expression measurements at a single-cell resolution and identification of reliable cellular heterogeneity, allowing for the identification of previously unrecognized levels of cellular heterogeneity, revealing regulatory relationships between genes, and tracking the trajectories of distinct cell lineages in the same or different developmental stages [63–66].”
From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [66]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredPrevious work spatially resolved four distinct basal stem cell populations within human IFE and delineated multiple spinous and granular cell populations contributing to a hierarchical differentiation lineage.
“we spatially resolved four distinct basal stem cell populations within human IFE and delineated multiple spinous and granular cell populations that contributed to a hierarchical differentiation lineage”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [27]
The Discussion reports at least four spatially distinct basal stem-cell populations in human neonatal epidermis and describes a differentiation hierarchy leading through spinous cells to granular keratinocytes. However, the Results section on epidermal heterogeneity identifies spinous clusters but describes granular keratinocytes as one GRN community, not multiple delineated granular populations. The claim also omits the neonatal restriction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHuman epidermis is more heterogeneous than previously thought.
“human epidermis is more heterogeneous than previously thought.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [27]
BAS-III cells typically sit atop the rete ridges in vivo, whereas BAS-IV cells lie at the bottom of rete ridges.
“BAS-III cells typically sit atop the rete ridges in vivo, whereas BAS-IV cells lie at the bottom of rete ridges.27”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [27]
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Tissue Mechanics in Haired Murine Skin: Potential Implications for Skin Aging
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The use of ectopic volar fibroblasts to modify skin identity
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Microbial metabolites control self-renewal and precancerous progression of human cervical stem cells
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Building vs. Rebuilding Epidermis: Comparison Embryonic Development and Adult Wound Repair
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Collagen XVII deficiency alters epidermal patterning
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Decoding the Human Epidermal Complexity at Single-Cell Resolution
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New insights into inflammatory memory of epidermal stem cells
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Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research
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LY6D marks pre-existing resistant basosquamous tumor subpopulations
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HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14
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SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation
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Self-citationDiversity of human skin three-dimensional organotypic cultures
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A single-cell transcriptome atlas of Lueyang black-bone chicken skin
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Epidermal/Dermal Separation Techniques and Analysis of Cell Populations in Human Skin Sheets
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Epigenetic regulation and signalling pathways in Merkel cell development
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Inflammatory Mediators Suppress FGFR2 Expression in Human Keratinocytes to Promote Inflammation
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Basal Cells in the Epidermis and Epidermal Differentiation
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A scalable, GMP-compatible, autologous organotypic cell therapy for Dystrophic Epidermolysis BullosaPreprint
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- Authors
- Wang, S., Drummond, M. L., Guerrero-Juarez, C. F., Tarapore, E., MacLean, A. L., Stabell, A. R., Wu, S. C., Gutierrez, G., That, B. T., Benavente, C. A., Nie, Q., & Atwood, S. X.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Nie, Qing
- Atwood, Scott X.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-08-25
- Volume
- 11
- Issue
- 1
- Pages
- 4239-4239
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7447770
- OpenAlex
- W3081219157
- Cited by
- 218
- References
- 131
- Citations by year
- 2026: 32 · 2025: 40 · 2024: 47 · 2023: 38 · 2022: 37 · 2021: 18 · 2020: 6
- FWCI
- 28.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Concern Foundation (CF204525)
- U.S. Department of Health & Human Services | National Institutes of Health (P30AR075047)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- basal stem cells, interfollicular epidermis, epidermal stratification, epidermal homeostasis, intercellular communication, pseudotime, RNA velocity, skin equivalents, rete ridges
- MeSH terms
- Epidermal Cells, Cell Communication, Cell Differentiation, Epidermis, Gene Expression Regulation, Homeostasis, Humans, Infant, Newborn, Male, Models, Biological, Stem Cells, Signal Transduction, Keratinocytes, Cell Lineage, Gene Expression Profiling, Foreskin
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