Single cell transcriptomics of human epidermis identifies basal stem cell transition states

Shuxiong Wang, Michael L. Drummond, Christian F. Guerrero-Juarez, Eric Tarapore, Adam L. MacLean, Adam R. Stabell, Stephanie C. Wu, Guadalupe Gutierrez, Bao T. That, Claudia A. Benavente, Qing Nie () and Scott X. Atwood ()
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Shuxiong Wang: University of California, Irvine
Michael L. Drummond: University of California, Irvine
Christian F. Guerrero-Juarez: University of California, Irvine
Eric Tarapore: University of California, Irvine
Adam L. MacLean: University of California, Irvine
Adam R. Stabell: University of California, Irvine
Stephanie C. Wu: University of California, Irvine
Guadalupe Gutierrez: University of California, Irvine
Bao T. That: University of California, Irvine
Claudia A. Benavente: University of California, Irvine
Qing Nie: University of California, Irvine
Scott X. Atwood: University of California, Irvine

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18075-7

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