Single-Cell and Spatial Transcriptome Analysis of Dermal Fibroblast Development in Perinatal Mouse Skin: Dynamic Lineage Differentiation and Key Driver Genes

Hanjae Lee; So Young Kim; Nak-Jung Kwon; Seong Jin Jo; Ohsang Kwon; Jong-Il Kim

doi:10.1016/j.jid.2023.11.008

Single-Cell and Spatial Transcriptome Analysis of Dermal Fibroblast Development in Perinatal Mouse Skin: Dynamic Lineage Differentiation and Key Driver Genes

J Invest Dermatol. 2023 Dec 9:S0022-202X(23)03127-5. doi: 10.1016/j.jid.2023.11.008. Online ahead of print.

Authors

Hanjae Lee¹, So Young Kim², Nak-Jung Kwon³, Seong Jin Jo⁴, Ohsang Kwon⁵, Jong-Il Kim⁶

Affiliations

¹ Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
² Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
³ Macrogen, Seoul, Korea.
⁴ Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea. Electronic address: oskwon@snu.ac.kr.
⁶ Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University, Seoul, Korea.

PMID: 38072389
DOI: 10.1016/j.jid.2023.11.008

Abstract

Several single-cell RNA studies of developing mouse skin have elucidated the molecular and cellular processes involved in skin development. However, they have primarily focused on either the fetal or early postnatal period, leaving a gap in our understanding of skin development. In this study, we conducted a comprehensive time-series analysis by combining single-cell RNA-sequencing datasets collected at different stages of development (embryonic days 13.5, 14.5, and 16.5 and postnatal days 0, 2, and 4) and validated our findings through multipanel in situ spatial transcriptomics. Our analysis indicated that embryonic fibroblasts exhibit heterogeneity from a very early stage and that the rapid determination of each lineage occurs within days after birth. The expression of putative key driver genes, including Hey1, Ebf1, Runx3, and Sox11 for the dermal papilla trajectory; Lrrc15 for the dermal sheath trajectory; Zfp536 and Nrn1 for the papillary fibroblast trajectory; and Lrrn4cl and Mfap5 for the fascia fibroblast trajectory, was detected in the corresponding, spatially identified cell types. Finally, cell-to-cell interaction analysis indicated that the dermal papilla lineage is the primary source of the noncanonical Wnt pathway during skin development. Together, our study provides a transcriptomic reference for future research in the field of skin development and regeneration.

Keywords: Developmental biology; Differentiation; Fibroblast; Single-cell analysis; Spatial analysis.