PT  - JOURNAL ARTICLE
AU  - Shuxiong Wang
AU  - Michael L. Drummond
AU  - Christian F. Guerrero-Juarez
AU  - Eric Tarapore
AU  - Adam L. MacLean
AU  - Adam R. Stabell
AU  - Stephanie C. Wu
AU  - Guadalupe Gutierrez
AU  - Bao T. That
AU  - Claudia A. Benavente
AU  - Qing Nie
AU  - Scott X. Atwood
TI  - Single cell transcriptomics of human epidermis reveals basal stem cell transition states
AID  - 10.1101/784579
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 784579
4099  - http://biorxiv.org/content/early/2019/09/30/784579.short
4100  - http://biorxiv.org/content/early/2019/09/30/784579.full
AB  - How stem cells give rise to human interfollicular 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 at least four spatially distinct stem cell populations that decorate the top and bottom of rete ridge architecture and hold transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling through co-variance of cognate ligand-receptor pairs indicate that the basal cell populations distinctly serve as critical signaling hubs that 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 the “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.