The nature of intestinal stem cells' nurture

The ‘nature versus nurture’ debate concerns the relative contributions to an individual's identity of its nature (that is, its genetic make‐up) compared with its nurture, defined as the totality of external, environmental factors. A similar type of debate is ongoing among developmental and stem‐cell biologists: is the intrinsic nature (that is, its (epi)genetic make‐up) of a stem cell what makes it self‐renew and differentiate according to the physiological needs of a given tissue, or is it the immediate environment (nurture) that regulates stemness? Irrespective of the relative weight of each contribution, there is little doubt that both cell‐autonomous and environmental factors play crucial roles in the maintenance of homeostasis in self‐renewing tissues such as the skin, mammary gland, blood and intestine. In an article published last month in EMBO reports (Mustata et al , 2011), the Lgr4 gene is shown to have a rate‐limiting role in establishing the stem‐cell niche of the proximal intestinal tract. > …the Lgr4 gene is shown to have a rate‐limiting role in establishing the stem‐cell niche of the proximal intestinal tract The epithelial lining of the proximal intestine is characterized by a unique tissue architecture consisting of villi and crypts. The intestinal crypt of Lieberkuhn is a highly dynamic niche with stem cells in its lower third, which give rise to a population of fast‐cycling transit‐amplifying cells. Transit‐amplifying cells undergo a limited number of cell divisions and eventually differentiate into four specialized cell types of the small intestine: absorptive, enteroendocrine, goblet and Paneth cells. Notably, Paneth cells are the only terminally differentiated cell type of the proximal intestinal tract that (i) move downwards along the crypt–villus axis and (ii) retain canonical Wnt signalling activity upon differentiation (van Es et al , 2005). On the basis of clonal analysis and knock‐in …