Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis.

Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA sequencing may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted single-cell RNA sequencing on keratinocytes from a mouse transgenic for the E7 gene of HPV16 and showed sensitive and specific detection of HPV16-E7 mRNA, predominantly in basal keratinocytes. We showed that increased E7 mRNA copy number per cell was associated with increased expression of E7 induced genes. This technique enhances detection of active viral transcription in solid tissue and may clarify possible linkage of HPV infection to development of squamous cell carcinoma.

Secreted immunoregulatory proteins in the skin.

The skin, thought initially to protect the body passively from pathogenic organisms and other environmental insults, is now recognised additionally as a sophisticated immune organ that actively regulates local immunity. Studies linking local innate and adaptive immunity to skin health and disease have revealed a complex network of cell communication and cytokine signalling. Here, we review the last 10 years of literature on this topic, and its relevance to skin immunity.

Mitotic Diversity in Homeostatic Human Interfollicular Epidermis.

Despite decades of skin research, regulation of proliferation and homeostasis in human epidermis is still insufficiently understood. To address the role of mitoses in tissue regulation, we utilized human long-term skin equivalents and systematically assessed mitoses during early epidermal development and long-term epidermal regeneration. We now demonstrate four different orientations: (1) horizontal, i.e., parallel to the basement membrane (BM) and suggestive of symmetric divisions; (2) oblique with an angle of 45°-70°; or (3) perpendicular, suggestive of asymmetric division. In addition, we demonstrate a fourth substantial fraction of suprabasal mitoses, many of which are committed to differentiation (Keratin K10-positive). As verified also for normal human skin, this spatial mitotic organization is part of the regulatory program of human epidermal tissue homeostasis. As a potential marker for asymmetric division, we investigated for Numb and found that it was evenly spread in almost all undifferentiated keratinocytes, but indeed asymmetrically distributed in some mitoses and particularly frequent under differentiation-repressing low-calcium conditions. Numb deletion (stable knockdown by CRISPR/Cas9), however, did not affect proliferation, neither in a three-day follow up study by life cell imaging nor during a 14-day culture period, suggesting that Numb is not essential for the general control of keratinocyte division.

Meeting report: the road to science-based policy - ESOF through the eyes of young scientists.

Communication and common understanding between politicians, scientists, and the society can lead to evidence-based science policy, a core principle that guides high caliber research and open innovation for a sustainable future.