Blocking TGF-β and BMP SMAD-dependent cell differentiation is a master key to expand all kinds of epithelial stem cells

Epithelia are widely found in human tissues where they play various functions, providing mechanical protection, regulating exchanges between a body cavity and the underlying tissue or secreting various molecules inside or outside the body. This plethora of epithelia is susceptible to a large number of inherited or sporadic diseases impacting their functions. To cite but a few, cystic fibrosis is an inherited autosomal recessive disorder due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene coding for a chloride ion channel (1). CFTR loss in lung, pancreas, liver kidney and intestine results in epithelia malfunctions, respiratory complications being the most life-threatening symptom of cystic fibrosis. Inherited mutations in the Breast Cancer susceptibility (BRCA) 1 or 2 tumor suppressor genes predispose to breast and ovarian cancers originating from epithelial cells transformation (2). The ability to grow normal and pathological primary human adult epithelial cells in culture and to subject them to genetic manipulations is then of paramount importance for the fundamental studies of these diseases and for the development of efficient treatments.