Binary organization of epidermal basal domains highlights robustness to environmental exposure

Adulte interfollicular epidermis (IFE) renewal is likely orchestrated by physiological demands of its complex tissue architecture comprising spatial and cellular heterogeneity. Mouse tail and back skin display two kinds of basal IFE spatial domains that regenerate at different rates. Here, we elucid...

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Bibliographic Details
Published in:The EMBO journal 2022-09, Vol.41 (18), p.e110488-n/a
Main Authors: Ghuwalewala, Sangeeta, Lee, Seon A, Jiang, Kevin, Baidya, Joydeep, Chovatiya, Gopal, Kaur, Pritinder, Shalloway, David, Tumbar, Tudorita
Format: Article
Language:English
Subjects:
Adaptation
Adult
Animal tissues
Animals
Cell differentiation
Cell Differentiation - genetics
Cell proliferation
Cell survival
Differentiation (biology)
Domains
Environmental Exposure
Epidermal Cells
epidermal domains
Epidermis
Exposure
Gene expression
Gene targeting
Heterogeneity
Homeostasis
human skin
Humans
Mice
Physiology
Ridges
Robustness
scRNA‐seq
Skin
Sox6
Survival
Tails
Transcriptomics
Ultraviolet radiation
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Summary:Adulte interfollicular epidermis (IFE) renewal is likely orchestrated by physiological demands of its complex tissue architecture comprising spatial and cellular heterogeneity. Mouse tail and back skin display two kinds of basal IFE spatial domains that regenerate at different rates. Here, we elucidate the molecular and cellular states of basal IFE domains by marker expression and single‐cell transcriptomics in mouse and human skin. We uncover two paths of basal cell differentiation that in part reflect the IFE spatial domain organization. We unravel previously unrecognized similarities between mouse tail IFE basal domains defined as scales and interscales versus human rete ridges and inter‐ridges, respectively. Furthermore, our basal IFE transcriptomics and gene targeting in mice provide evidence supporting a physiological role of IFE domains in adaptation to differential UV exposure. We identify Sox6 as a novel UV‐induced and interscale/inter‐ridge preferred basal IFE‐domain transcription factor, important for IFE proliferation and survival. The spatial, cellular, and molecular organization of IFE basal domains underscores skin adaptation to environmental exposure and its unusual robustness in adult homeostasis. Synopsis Adult skin interfollicular epidermis (IFE) serves as an essential body barrier to environmental insults, yet its composition and renewal mechanisms remain debated. This work identifies two distinct spatial domains of the basal IFE in mouse and human, suggesting tissue adaptation to differential environmental challenges. Cell tracing combined with single‐cell expression profiling uncovers two IFE basal domains with distinct gene expression patterns and cell differentiation paths in the mouse tail. IFE scale and interscale domains contain comparable mixtures of stem, proliferating, and differentiating basal cell type states. Basal IFE domain organization is shared between mouse tail and human. Sox6 is enriched in more UV‐exposed IFE regions and is required for basal cell proliferation and survival during homeostasis and acute UV exposure. Adult interfollicular epidermis in mouse and human shows unexpected spatial and molecular heterogeneity, suggesting adaption to differential environmental challenges.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.15252/embj.2021110488