The first atlas of human skin shows how to reconstruct skin without scars

2024-10-16 15:00:00

The first cell atlas of prenatal human skin development has just been presented by an international team of scientists, led by the Welcome Sanger Institute and the Newcastle University (UK) represents an unprecedented milestone in developmental biology. Published in the magazine ‘Nature‘, the atlas offers a new understanding of how skin and hair follicles (where hair grows) are formed before birth.

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 grows in a sterile environment inside the uterus. Before birth, it not only performs its function as a protective barrier and regulator of 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, as new follicles are not created after birth, although a renewal cycle occurs in existing ones. Until now, it has been difficult to study this process in depth due to the limitations of animal models, which have fundamental differences compared to human development.

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

This allowed us to describe the specific stages through which human hair follicles form and to observe the differences compared to mouse follicles. Furthermore, 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 fabricated a “mini organ” in the laboratory organoid of leather. Using adult stem cells, they managed to make this organoid develop the ability to grow hair, making it an unprecedented model for studying prenatal skin and its regenerative characteristics. Comparing the organoids to prenatal skin, they found that these models resembled pre-natal skin more than adult skin, underscoring their usefulness for future research.

However, the team found that blood vessels do not form in 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 vessels develop in organoids.

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

Furthermore, researchers have shown that macrophages are essential to the ability of prenatal skin to repair wounds without leaving scars. This paves the way for possible clinical applications that prevent scarring after surgery or injury.

Epidermal damage due to toxic epidermal necrolysis

T. Nordmann

Likewise, the Prenatal Cell Atlas offers an invaluable resource for the study of various congenital skin diseases, cLike butterfly skin or epidermolysis bullosa. Researchers have identified that genes associated with these diseases are active in prenatal skin, suggesting that these conditions have their origins before birth. Thanks to the precision of the atlas, scientists can now map which specific cells express 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 in laboratory conditions, enabling the development of more effective and personalized therapies. These organoid models could be applied in the creation of new hair follicles for people with cicatricial alopecia, or used in skin transplants for burn victims, where complete regeneration of the skin, including the follicles, is critical for aesthetic and functional recovery.

“The Cell Atlas of Human Prenatal Skin allowed us to provide the first ‘molecular recipe’ for building human skin, revealing how hair follicles are formed before birth,” he explains. Elena Winheimco-lead author of the study. “These discoveries have incredible clinical potential, as they could be used in regenerative medicine, skin and hair transplants, such as those needed for burn victims or people with healing alopecia.”

For his part, Hudaa Gopeefrom the University of Newcastle, adds: “We are thrilled 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 they may have clinical applications to avoid scarring after surgery.

Human Cell Atlas Project

This study is part of the ambitious project Atlas of human cellswhich seeks to map every cell of the human body to transform our understanding of health and disease. The researchers believe 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 making great strides toward creating a tool that allows us to better understand how the human body is built and what goes wrong in various diseases. Furthermore, the 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.