Human skin map gives ‘recipe’ for building skin and could help prevent scarring

For the first time, researchers have created a single-cell atlas of prenatal human skin to understand how skin forms and what goes wrong in disease.

Researchers from Newcastle University’s Wellcome Sanger Institute and their collaborators used single cell sequencing and other genomic techniques to create the atlas and discover how human skin, including hair follicles, forms. This knowledge could be used to create new hair follicles in regenerative medicine and in skin grafts for burn victims.

In the study, published October 16 in Naturethe team also created a “mini-organ” of skin in a dish with the ability to grow hair. Using the organoid, they showed how immune cells play an important role in scar-free skin repair, which could lead to clinical applications for preventing scarring after surgery or scar-free healing after injury. .

As part of the Human Cell Atlas, which maps all cell types in the human body to transform the understanding of health and disease, researchers propose a molecular “recipe” for building skin and a new organoid model for study congenital skin diseases.

The skin is the largest organ in the human body, measuring on average two meters square. It constitutes a protective barrier, regulates our body temperature and can regenerate itself. Skin develops in the sterile environment of the uterus, and all hair follicles form before birth. There is a follicular cycle after birth, but no new follicles are created. Before birth, the skin has the unique ability to heal without scarring.

It has been very difficult to study human skin development because animal models have key differences. As part of the Human Cell Atlas, a team of researchers is focusing on studying the construction of human skin. Understanding how skin develops, where cells are located in space and time, and the role of genetics will help reveal how specific mutations cause congenital skin disorders, such as bladder disorders and scaly skin.

In this new study, researchers from the Wellcome Sanger Institute at the University of Newcastle and their collaborators created the first single-cell, spatial atlas of human prenatal skin.

The team used prenatal skin tissue samples, which they broke down to examine individual cells in suspension, as well as cells in place in the tissue. The scientists used cutting-edge single-cell sequencing and spatial transcriptomics to analyze individual cells in space and time, as well as the cellular changes that regulate the development of skin and hair follicles. They described the steps that describe the formation of human hair follicles and identified the differences compared to mouse hair follicles.

Using adult stem cells, researchers also created a “mini-organ” of skin in a plate, called an organoid, with the ability to grow hair. They compared the molecular characteristics of the skin organoids with those of prenatal skin and found that the skin organoid model resembled prenatal skin more than adult skin.

The team found that blood vessels did not form in the skin organoid or in prenatal skin. By adding immune cells called macrophages to the organoid, they found that the macrophages promoted blood vessel formation, and the team undertook 3D imaging to assess blood vessel formation in the tissue.

These immune cells are known to protect the skin from infections. However, this is the first time that macrophages have been shown to play a key role in the formation of human skin early in development by promoting blood vessel growth. This provides an option to improve the vascularization of other tissue organoids.

The team also analyzed differences in cell types between prenatal and adult skin. They show how macrophages play an important role in scarless skin repair of prenatal skin, which could lead to clinical applications to prevent scarring after surgery or injury.

As a result of this study, the team proposes a molecular “recipe” for how human skin is constructed and how hair follicles form. This knowledge could be used in the creation of new hair follicles for regenerative medicine, such as for skin grafts in burn victims or those suffering from scarring alopecia.

The prenatal human skin atlas will also be used to identify in which cells genes are active or expressed that are known to cause congenital hair and skin disorders, such as bladder disorders and scaly skin. Researchers have discovered that the genes involved in these disorders are expressed in prenatal skin, meaning they originate in the uterus. The skin organoids created in this study offer a new and precise model for studying these diseases.

Dr Elena Winheim, co-first author from the Wellcome Sanger Institute, said: “With our prenatal atlas of human skin, we have provided the first molecular ‘recipe’ for making human skin and discovered how human hair follicles form. before birth. This knowledge has astonishing clinical potential and could be used in regenerative medicine, to offer skin and hair transplants, for example for burn victims or those suffering from scarring alopecia.

Co-first author Dr Hudaa Gopee from Newcastle University said: “We are delighted to have created a skin organoid model that grows hair. In this process, we discovered an important new role of immune cells in promoting hair growth. “

Professor Muzlifah Haniffa, co-lead author and Acting Head of Cellular Genetics at the Wellcome Sanger Institute, said: “Our prenatal human skin atlas and organoid model provide the research community with freely available tools to study the congenital skin diseases and explore the possibilities of regenerative medicine. We are making exciting progress toward creating the Human Cell Atlas, understanding the biological stages of how humans are built, and investigating what goes wrong in disease.