We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. By using antibodies to protein markers of each cell line, including some that are expressed early in the differentiation process, we aimed to study lineage development in this patient. From our data, we surmise that there may be a two-step process in lineage commitment. The stem cell may commit to an absorptive cell or a granule-containing cell. The intestinal crypts contain a population of multipotential stem cells from which all of the epithelial cell lineages are derived. On the basis of work in mice, a common progenitor cell located near the base of the crypt of Lieberkühn is thought to give rise to all four intestinal cell lines: absorptive enterocytes as well as Paneth, goblet, and enteroendocrine cells (1-4). Much work has been done to understand the differentiation and development from stem cells to the various terminally differentiated cell types of the intestinal epithelium and the factors that play a part in this process. Many factors have been implicated in this process, such as Wnt/-catenin signaling (5); Notch signaling, including the transcription factors Math1 (6) and Hes1 (7); homeobox transcription factors Cdx1 and Cdx2 (8); Kruppel-like factors KLF4 and KLF5 (9 -11); transcription factor Elf3 (12); platelet-derived growth factor (PDGF) A and its receptor, PDGF-Ra; the winged helix transcription factor Fkh6; the homeodomain transcription factor Nkx2-3; and Hox and ParaHox cluster genes, Sonic hedgehog, and bone morphogenetic proteins (13).Intestinal differentiation is difficult to study because of the technical challenge of growing nonmalignant epithelial cells in vitro. Although much has been learned from the use of normal, chimeric, and transgenic mice models, the process is still very ill defined. The work of Cheng and Leblond (2) on mouse models introduced the idea that the stem cell is the direct progenitor of each of the terminal lineages.We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. These lineages have in common Received November 17, 2004; accepted February 3, 2005
