The first-ever single cell atlas of the human skin and most advanced 'mini skin model' have been developed to aid in understanding skin formation and the mechanisms behind skin disorders.

In order to create the prenatal skin atlas, scientists used advanced techniques such as single-cell sequencing and special transcriptomics on prenatal skin tissue samples. These techniques were able to provide information about gene expression at specific locations within a tissue, allowing the scientists to track individual cells in suspension as well as cells intact within the tissue over time. They discovered the cellular changes that drive skin and hair follicle development.

'With our prenatal human skin atlas, we've provided the first molecular "recipe" for making human skin and uncovered how human hair follicles are formed before birth' said Dr Elena Winheim, co-lead author of the paper published in Nature and post doctoral fellow at the Wellcome Sanger Institute, near Cambridge.

The skin is the body's largest organ and serves as a protective barrier, regulates body temperature and can regenerate itself. Skin develops in the sterile environment of the womb, where all hair follicles are formed before birth. While hair grows in cycles after birth, no new follicles are formed. Furthermore, before birth, skin has the unique ability to heal without scarring.

The researchers also used adult stem cells to create a 'mini organ' of skin in a dish, known as an organoid, which had the ability to grow hair. The team used the organoid to show that immune cells contribute to scarless skin repair, potentially leading to clinical strategies for preventing scarring after surgery or achieving scarless healing after wounding.

This project is part of the Human Cell Atlas initiative, which aims to create comprehensive maps of all cell types in the human body (see BioNews 946, 1185, 1193, 1234 and 1254). The goal is to identify the cellular basis of health and disease, and to better understand how the human body functions.

Researchers from the Wellcome Sanger Institute, Newcastle University and their collaborators compared the molecular characteristics of skin organoids with prenatal skin and found the skin organoid model more closely resembled prenatal skin than adult skin.

However, they discovered that blood vessels did not form as effectively in the skin organoid compared to prenatal skin. Yet, blood vessel formation was promoted when the scientists added macrophages (a type of white blood cell that kills pathogens) to the organoid. The team used 3D imaging to study this process in the tissue.

Though macrophages are known to protect against infections, this is the first time they have been shown to play a role in skin formation during early development. The scientists believe that this discovery could help improve blood vessel formation in other type of tissue organoids.

Differences in cell types between prenatal skin and adult skin also highlighted the role of macrophages in scarless skin repair in prenatal skin, which could pave the way for clinical applications designed to prevent scarring following surgeries or injuries.

'These insights have amazing clinical potential and could be used in regenerative medicine, when offering skin and hair transplants, such as for burn victims or those with scarring alopecia,' Dr Winheim said.

The team has identified that genes associated with congenital hair and skin disorders, like blistering and scaly skin conditions, are active in prenatal skin, suggesting they originate in the womb. Thus, the skin organoids developed in this study may provide a new and precise model for researching these diseases.