title: Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity.
abstract: The murine epidermis with its hair follicles represents an invaluable model system for tissue regeneration and stem cell research. Here we used single-cell RNA-sequencing to reveal how cellular heterogeneity of murine telogen epidermis is tuned at the transcriptional level. Unbiased clustering of 1,422 single-cell transcriptomes revealed 25 distinct populations of interfollicular and follicular epidermal cells. Our data allowed the reconstruction of gene expression programs during epidermal differentiation and along the proximal-distal axis of the hair follicle at unprecedented resolution. Moreover, transcriptional heterogeneity of the epidermis can essentially be explained along these two axes, and we show that heterogeneity in stem cell compartments generally reflects this model: stem cell populations are segregated by spatial signatures but share a common basal-epidermal gene module. This study provides an unbiased and systematic view of transcriptional organization of adult epidermis and highlights how cellular heterogeneity can be orchestrated in vivo to assure tissue homeostasis.
authors.affiliation: Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Joost
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden.
authors.forename: Amit
authors.initials: A
authors.lastname: Zeisel
authors.affiliation: Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors.forename: Tina
authors.initials: T
authors.lastname: Jacob
authors.affiliation: Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden.
authors.forename: Gioele
authors.initials: G
authors.lastname: La Manno
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lönnerberg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden. Electronic address: sten.linnarsson@ki.se.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden. Electronic address: maria.kasper@ki.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Kasper
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004817:Epidermis; D005260:Female; D018859:Hair Follicle; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells; D059467:Transcriptome