Human life unfolds through distinct stages, beginning at conception and progressing into old age. This intricate journey encompasses biological, physiological, and psychological transformations. These developmental phases are typically divided into the prenatal period, infancy, childhood, and adolescence, each defined by unique features and dynamics that evolve under the influence of both biological and environmental factors.
A study by Gopee et al. focused on understanding the cellular and molecular mechanisms involved in skin and hair follicle (HF) morphogenesis during prenatal development. By employing advanced techniques such as single-cell RNA sequencing, spatial transcriptomics, and multiplexed RNA in situ hybridization, the researchers developed a detailed multi-omics atlas of human prenatal skin covering gestational weeks 7 to 17. Comparison of this atlas with a skin organoid model derived from human pluripotent stem cells highlighted the absence of immune cells and reduced endothelial cell diversity and abundance in the organoid. Adding autologous macrophages to the organoid culture significantly enhanced vascular remodeling, emphasizing the role of macrophages in skin angiogenesis.
The infancy period, which covers the first two years after birth, is characterized by rapid growth and development, particularly in brain and motor functions, reflecting heightened environmental sensitivity. This stage is followed by childhood (ages 2–12), during which cognitive abilities notably advance, and adolescence, which bridges the transition to young adulthood with physical, hormonal, and emotional changes, including identity formation. Among these stages, the prenatal period plays a foundational role, shaping biological structures and initiating the functional development of organ systems. During this phase, the skin develops not only as a physical barrier but also as a critical immune defense, safeguarding newborns against environmental threats and microorganisms.
Skin development during the prenatal period is vital for establishing an effective postnatal immune system. Langerhans cells, located in the epidermis, work in tandem with keratinocytes to recognize foreign substances and trigger immune responses after birth. This interaction enables the formation of a chemical defense system that ensures quick and efficient responses to pathogens.
The prenatal organization of skin layers, including the epidermis, dermis, and hypodermis, positions immune cells strategically to build the skin’s primary defense barrier. However, research reveals that prenatal skin development extends beyond immunity, playing a key role in tissue formation. Immune cells like macrophages significantly contribute to the creation of a supportive microenvironment essential for tissue development in embryonic skin.
Studies investigating immune cells’ roles in skin have leveraged single-cell RNA sequencing (scRNA-seq) to map immune (CD45+) and non-immune (CD45−) cell profiles in prenatal skin. Combined with spatial transcriptomic data, these studies demonstrate that immune cells not only defend but actively contribute to tissue formation. During this period, LYVE1+ and TREM2+ macrophages engage with endothelial cells, aiding in vascular network formation and supporting hair follicle and vascular structure development. Artificial skin models (SkO) compared with prenatal skin reveal a lack of immune cells and reduced endothelial diversity in the models. However, introducing macrophages restores vascular network development, highlighting their crucial role in prenatal angiogenesis.
In conclusion, prenatal skin development takes place in a dynamic microenvironment supported by immune cells, where it not only establishes essential defense mechanisms but also facilitates tissue formation. This research underscores the multifaceted functions of immune cells in prenatal skin morphogenesis, hair follicle formation, and scarless wound healing while highlighting the potential of SkO models in advancing skin biology and disease research.
Author: Birgül Sarı
Editor: Fatma Duran
Reference: Gopee, N.H., Winheim, E., Olabi, B., et al. (2024). A prenatal skin atlas reveals immune regulation of human skin morphogenesis. Nature, DOI: https://doi.org/10.1038/s41586-024-08002-x
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News articles prepared by our team members, reviewing and compiling scientific research published in journals with an impact factor greater than 20 (click here for the list).