Langerhans cells (LCs) are antigen-presenting cells of the epidermis, and play a key role in detecting pathogens in the skin and coordinating the immune response. However, the precursors of LCs during embryonic development are poorly characterised, particularly in humans. Here (), Adelheid Elbe-Bürger and colleagues analyse the characteristics of early LC precursors in human first-trimester foetal skin, and explore the potential of different populations of haematopoietic precursors to colonise the developing epidermis. They find an unexpected diversity in LC precursors in terms of cell-surface markers, contrasting with the homogeneous adult LC population. The authors then used in vitro skin equivalent cultures to test the ability of different cord blood-derived precursor populations to colonise the epidermis and differentiate as LCs. Various precursor subtypes show LC potential, and the data suggest that the skin equivalents produce those signals necessary to direct LC differentiation. Together, these data suggest a heterogeneous origin for human embryonic LC precursors during early stages of development.
