**1. Introduction**

The development of human three-dimensional (3D) organoids by bioengineering now permits these models to make an increasing contribution to deciphering developmental processes, tissue and organ physiology and pathophysiological contexts. Notably, achievements have been reported with heart organoids in the domain of myocardial infarction and drug cardiotoxicity [1], with brain organoids for studies of hypoxic brain injury and prematurity [2] and medulloblastoma modeling [3], with liver organoids for studies of normal [4] and cancer [5] development, and with organoids modeling normal and cancer contexts in the digestive tract [6,7]. In skin, human 3D organoids have demonstrated efficiency in the modeling of pathophysiological contexts, such as defects in the epidermal barrier associated with atopic dermatitis [8], or epidermal cancer proneness in xeroderma pigmentosum [9]. Notably, bioengineered 3D epidermises have contributed to the knowledge of keratinocyte stem and progenitor cells [10–13].

Today, deciphering the adverse impacts of normal tissue exposure to low radiation doses constitutes a biomedical research field of growing interest, due to their increasing use in medical diagnosis technologies such as computed tomography (CT) scans, for both adult and pediatric patients [14,15]. Radiotherapy (RT) is also a source of low-dose exposure for normal tissues and organs surrounding the targeted tumor. As the number of cancer survivors and their lifespans increase thanks to constant improvement of diagnostic methods and medical management, the problem of RT complications is becoming a medical issue of growing importance. Skin is of particular concern regarding RT adverse reactions, as this organ can develop different types of short- and long-term radio-pathologies [16]. Our group and I. Turesson's group in Sweden have shown that human skin, and notably the epidermis, can develop different types of complications after exposure to high [17] or low [18,19] radiation doses, complications such as erythema, epidermitis, dysplasia, as well as acanthosis and carcinoma in the long-term. However, the contributions of specific target cell populations in these pathophysiological processes still require in-depth studies.

Here, we have investigated the effects of low radiation doses on the capacity of keratinocyte stem and progenitor cells to ensure epidermis regeneration, and have explored the cellular perturbations at the origin of radio-induced disorders that can affect this tissue. We show that pre-transplantation exposure of keratinocyte precursor cells to a single dose of 50 mGy, at the initial stage of 3D epidermis generation, induced focal dysplasia in xenografted epidermises, exhibiting characteristics of epithelialto-mesenchymal transition (EMT).
