First human skin atlas shows how to rebuild skin without scars

But it could also have important applications for the treatment of burns, scars and congenital skin diseases.

The skin is the largest organ in the human body and develops in a sterile environment inside the womb. Before birth, it not only fulfills its function as a protective barrier and regulates body temperature, but also has the ability to regenerate without leaving scars, a characteristic that is lost after birth.

All hair follicles are formed during this prenatal period, since new follicles are not created after birth, although a renewal cycle does occur in existing ones. Until now, it has been difficult to study this process in depth due to the limitations of animal models, which have key differences from human development.

To overcome these barriers, the research team led by Muzlifah Haniffainterim director of Cellular Genetics at the Wellcome Sanger Instituteused a method called single-cell sequencing and advanced spatial transcriptomics techniques, which allow cells to be analyzed within their spatial and temporal context in the tissue.

This allowed us to describe the specific steps by which human hair follicles are formed and to observe differences compared to mouse follicles. Additionally, by using prenatal skin samples, they were able to create the first cellular and spatial atlas documenting this process, providing a ‘molecular recipe‘ of how human skin is constructed.

In this work, the researchers manufactured a ‘mini organ’ in the laboratory organoid of skin. Using adult stem cells, they managed to make this organoid develop the ability to grow hair, making it an unprecedented model to study prenatal skin and its regenerative characteristics. When comparing the organoids to prenatal skin, they found that these models more closely resembled skin before birth than adult skin, underscoring their usefulness for future research.

However, the team found that blood vessels did not form in the organoids in the same way as in prenatal skin. By adding macrophages, a type of immune cell, they observed that they promoted the formation of blood vessels, which led them to perform three-dimensional imaging to evaluate how the vessels developed in the organoids.

This finding has other implications, as it shows that macrophages not only protect the skin against infection, but also play a key role in its early formation, supporting the growth of blood vessels. This discovery could be useful to improve vascularization in other types of organoids and tissues created in the laboratorywhich could impact various fields of regenerative medicine.

Additionally, the researchers demonstrated that macrophages are essential in the ability of prenatal skin to repair wounds without scarring. This opens a path for possible clinical applications that prevent scars after surgeries or injuries.

Likewise, the prenatal cell atlas offers an invaluable resource for studying various congenital skin diseases, cLike butterfly skin or epidermolysis bullosa. The researchers identified that the genes associated with these diseases are active in prenatal skin, suggesting that these conditions have their origin before birth. Thanks to the precision of the atlas, scientists can now map which specific cells express the genes related to these diseases, facilitating a better understanding of their development and, potentially, new avenues for their treatment.

The ability to create skin organoids that resemble prenatal skin also provides a more accurate model for studying these diseases under laboratory conditions, allowing for the development of more effective, personalized therapies. These organoid models could be applied in the creation of new hair follicles for people with scarring alopecia, or used in skin transplants for burn victims, where complete skin regeneration, including follicles, is critical for aesthetic and functional recovery. .

“The cellular atlas of human prenatal skin has allowed us to provide the first ‘molecular recipe’ for the construction of human skin, revealing how hair follicles form before birth,” he explains. Elena Winheimco-lead author of the study. “These discoveries have incredible clinical potential, since they could be used in regenerative medicine, in skin and hair transplants, such as those necessary for burn victims or people with scarring alopecia.”

For its part, Hudaa Gopeefrom the University of Newcastle, adds: ‘We are excited to have created a skin organoid model. In this process, we discovered a crucial new role of immune cells in promoting blood vessel growth in developing skin, which could improve other organoid models. These macrophages also appear to play a key role in prenatal skin repair, which could have clinical applications to avoid scars after surgeries.

Human Cell Atlas Project

This study is part of the ambitious project Human Cell Atlaswhich seeks to map every cell in the human body to transform our understanding of health and disease. The researchers are convinced that this prenatal skin atlas and organoid model will have a lasting impact on scientific research and clinical medicine by providing accessible and accurate tools to study skin diseases and explore new possibilities in regenerative medicine.

“Our prenatal human skin atlas and organoid model provide freely accessible tools to study congenital skin diseases and explore the possibilities of regenerative medicine,” emphasizes Haniffa.

With this research, scientists are taking big steps toward creating a tool that allows us to better understand how the human body is built and what goes wrong in various diseases. Furthermore, cell atlas and skin organoids offer a promising platform to develop more effective treatments for congenital diseases and to improve tissue regeneration techniques in patients with severe skin damage.