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Cell Syst. 2016 Sep 28;3(3):221-237.e9. doi: 10.1016/j.cels.2016.08.010. Epub 2016 Sep 15.

Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity.

Author information

1
Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
2
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden.
3
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden. Electronic address: sten.linnarsson@ki.se.
4
Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden. Electronic address: maria.kasper@ki.se.

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.

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