Since December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged in Wuhan, Hubei, China, as an etiological agent causing a new infectious respiratory disease, coronavirus disease 2019, which manifests as fever, severe respiratory illness, and pneumonia (Huang et al., 2020). With significant morbidity and mortality, coronavirus disease 2019 has now evolved into a global pandemic (Park, 2020). To date, more than 3 million cases of coronavirus disease 2019 have been reported worldwide, including 252,336 deaths, according to the World Health Organization. The entry of coronavirus into target cells mainly depends on the binding of the viral spike proteins to cellular receptors (Hoffmann et al., 2020). ACE2 has been identified as a crucial functional receptor of SARS-CoV-2 (Wang et al., 2020). The receptor-binding domain of the SARS-CoV-2 spike protein was reported to have a strong interaction with human ACE2 molecules, which was confirmed in molecular structure (Wrapp et al., 2020; Xu et al., 2020b). These studies suggested that the ACE2-expressing cells were vulnerable to SARS-CoV-2 infection. The RNA and protein expressions of ACE2 have been widely investigated by bulk samples from the heart, lung, kidney, and other organs (Hamming et al., 2004). Recently, single-cell RNA sequencing (scRNA-seq) was applied to analyze ACE2 mRNA expression in different cell subtypes. High ACE2 expression was identified in type II alveolar cells, bronchial transient secretory cells, small intestinal epithelium cells, and oral epithelial cells in accordance with respiratory clinical manifestations and rare clinical manifestations such as gastrointestinal symptoms, suggesting the respiratory droplet, digestive, and fecal-oral transmission routes of SARS-CoV-2 (Liang et al., 2020; Lukassen et al., 2020; Xu et al., 2020a). Therefore, we hypothesized that the expression and distribution of ACE2 in human organs and tissues could reflect the potential infection routes of SARS-CoV-2. However, scRNA-seq has not yet been applied to examine ACE2 expression in the cells of skin tissues, and the transmission of this virus by percutaneous routes remains unclear. To investigate whether skin was a potential target for SARS-CoV-2 infection, we first analyzed ACE2 mRNA expression and ACE2-positive cell composition in skin tissues based on public databases(GEPIA2 and ARCHS4) and found that ACE2 was expressed in skin tissues in addition to testis, kidney, colon, lung, and so on. The expression of ACE2 was significantly higher in keratinocytes than other cell types in skin tissues, such as fibroblasts and melanocytes (Figure 1a and b). Moreover, our in-house data of bulk RNA sequencing from 18 skin samples showed ACE2 expression in all samples (Figure 2a), which was further validated by quantitative real-time RTPCR (Ct ¼ 28.97 Æ 1.91, Figure 2b). We then performed scRNA-seq to evaluate the cell typeespecific expression of ACE2 in six skin samples. After data processing, 40,459 cells were acquired and eight cell types were identified based on their canonical markers, including keratinocytes(KRT1 þ, KRT5 þ, KRT10 þ, and KRT14 þ), endothelial cells (SELE þ and CD93 þ), fibroblasts(DCN þ, COL6A1 þ, and COL6A2 þ), hair follicles (SOX9 þ), immune cells (PTPRC þ, IL32 þ, and CD3D þ), lymphatic endothelial cells (CCL21 þ and LYVE1 þ), melanocytes (TYRP1 þ and PMEL þ), and sweat gland cells (DCD þ, KRT19 þ, KRT7 þ, and AQP5 þ)(Figure 2c). We found that 0.19% of skin cells in all six samples were ACE2-positive. Among these positive cells, keratinocytes were most enriched, accounting …