The intestinal epithelium is a rapidly renewing tissue that can undergo complete cellular replacement every four to five days due to the presence of intestinal stem cells (ISCs), which exist at the intestinal crypt base and give rise to the full diversity of cell types present in the adult intestinal epithelium.1 See More These regenerative properties make the intestinal epithelium an attractive system for researchers studying intestinal development, stem cell biology, digestive diseases and cancer.
The intestinal stem cell niche is located in the crypt base where the LGR5+ ISCs reside intercalated by Paneth cells.2 Paneth cells help to maintain the stem cell niche and are also involved in the innate immune response. ISCs divide and increase their population while traveling towards the villus and central lumen, during the transit amplification phase. Upon leaving the intestinal crypt, they terminally differentiate into one of three major cell types: goblet cells, which secrete mucus to protect the epithelial lining and help move intestinal contents through the lumen; enteroendocrine cells, which secrete hormones to regulate nutrient metabolism; and enterocytes, which form the majority of the intestinal epithelium and are responsible for nutrient absorption.3
New advances in intestinal research have led to the development of a 3D model system known as intestinal organoid culture. Intestinal organoids are multicellular structures that retain key features of the adult intestinal epithelium including the crypt-villus morphology, a functional central lumen and all of the major cell types listed above.4 This physiologically relevant and convenient in vitro model system has already been demonstrated to be a powerful tool for disease modeling, drug screening and personalized medicine.about this culture system.
- van der Flier LG & Clevers H. (2009) Annu Rev Physiol 71: 241-60
- Barker N, et al. (2007) Nature 449(7165): 1003-7
- Clevers H & Batlle E. (2013) Cell 152(5): 1198
- Sato T, et al. (2009) Nature 459(7244): 262-5
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Generation of Mouse and Human Organoid-Forming Intestinal Progenitor Cells by Direct Lineage Reprogramming
Scientists showed that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs formed spherical organoids that developed into adult-type budding organoids containing cells with intestinal stem cell properties.Intestinal Cell News Volume 3.36, September 22, 2017. Read full issue at