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Studies on molecular mechanisms of self-renewal in normal stem cells are required for understanding the cancer stem cell. Self-renewal in many kinds of normal stem cells might be accelerated in the growth of a young organism and in the repair of damaged tissue. This study examined whether the esophagus in growing neonates provides an experimental system for studies on epithelial stem cell renewal. The esophageal epithelium consists of 3 layers, from the luminal side to the bottom: the differentiated, epibasal and basal cell layers. The basal cell layer is known to contain the stem cells for the esophageal epithelium. This basic architecture is observed both in mice and humans. We investigated the basal cells in the mouse neonate by immunostaining with a basal cell marker, nerve growth factor receptor (Ngfr), and compared the basal cell content in the esophageal epithelium between mice and humans. A mouse esophageal epithelial cell primary culture system was developed for studies on the basal cell growth and keratinocyte differentiation, and microarray analysis was conducted for obtaining expression profiles of the basal cells. It was revealed that the growth of the esophageal epithelium begins from postnatal day 3, and that the timing is consistent with membrane localization of Ngfr in the basal cell. An increase in the basal cell number by Ngf treatment is observed in in vitro mouse esophageal epithelium cultures. Furthermore, mRNA overexpression of Pdgfrb encoding platelet derived growth factor receptor beta and Egfr encoding epidermal growth factor receptor is associated with the timing of the growth of the esophageal epithelium in the neonatal mice. This study provides a new experimental model for studies on the growth of the basal cells, which are considered to include the stem cells, and on the enlargement of the body size in young organisms.

Molecular profiles of the mouse postnatal development of the esophageal epithelium showing delayed growth start