First human skin map provides ‘recipe’ that could prevent scarring and make hair transplants easier

The skin is the largest organ in the human body, measuring an average of two square meters. It constitutes a protective barrier, regulates our body temperature and can regenerate itself.

But I bet you didn’t know that 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.)

Most importantly for the scientists behind a new report, before birth, skin has the unique ability to heal without leaving scars.

Now, 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 – information that could be used to create new follicles hair in regenerative medicine and in transplants for burn victims.

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.

For the study, published in Nature, the team also created a “mini-organ” of skin in a dish with the actual 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 surgery. an injury.

“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,” said Dr. Elena Winheim, co-first author of the paper. Wellcome Sanger Institute.

As part of the Human Cell Atlas, which maps all cell types in the human body to transform the understanding of health and disease, the research deepens our understanding of skin development, the position of cells in space and time, and the role of genetics in revelation. how specific mutations cause congenital skin disorders, such as bladder disorders and scaly 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. (One reason it is so difficult to study human skin development is that animal models are very different.)

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. But, by adding immune cells called macrophages to the organoid, they discovered, through 3D imaging, that the macrophages promoted the formation of blood vessels.

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 vascularization of other tissues, which could lead to clinical applications to prevent scarring after surgery or injury.

“This knowledge has incredible clinical potential and could be used in regenerative medicine, including offering skin and hair transplants, for example for burn victims or those suffering from scarring alopecia,” said Dr Winheim.

“We are delighted to have created an organoid model of skin that grows hair. In this process, we discovered an important new role for immune cells in promoting blood vessel growth,” said co-first author Dr Hudaa Gopee from Newcastle University. “Our findings could inform clinical advances to prevent scarring after surgery.”

Learn more about how the team grows skin organoids in the lab in this Sanger Institute blog post.