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Absorptive cellsEnterocyte: nutrient absorption
Secretory cellsGoblet cell: mucus secretionPaneth cells: antimicrobial product secretionEnteroendocrine cells: hormone secretion
OtherTuft cellsM-cells
Cells proposed to be derived from ISCs at the crypt base
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Colon similar to small intestine:Similar cell types are derived from ISCs at the crypt base
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Labeling proliferating cells and following their migration: ~5 days from birth to death
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ISCs – Crypt base columnar (CBC) cells or +4 cells?
+4 cells were proliferating, label-retaining cells: proposed to possess an immortal DNA strand maintained by asymmetric cell division
CBC cells were traced to all the lineages and formed crypts when cultured ex vivo
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Barker N. et al, Nature 449:1003, 2007
Lgr5 expressionMarks CBCs
Lgr5 expression restricted to CBC cells
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Use of an Lgr5-GFP-Cre transgene to mark Lgr5-expressing cells and their descendents
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1 5 60 days following Cre activation
Use of an Lgr5-GFP-Cre transgene to mark Lgr5-expressing cells and their descendents
CBC stem cells mapping below +4
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T Sato et al. Nature 000, 1-4 (2009) doi:10.1038/nature07935
Single Lgr5+ cells generate crypt–villus structures.
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T Sato et al. Nature 000, 1-4 (2009) doi:10.1038/nature07935
Composition of single stem cell-derived organoids.
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Barker N. et al, Nature 449:1003, 2007
Fun facts: Lgr5 ISCs do not undergo asymmetric division – they divide symmetrically, producing either 2 TA cells or 2 ISCs.
No evidence of an immortal DNA strand in Lgr5 ISCs obtained
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An Lgr5-Diptheria toxin receptor fusion gene can trigger the elimination of Lgr5-expressing cells
Tian et al. Nature 2011
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Crypts develop normally even when Lgr5 cells depleted
Tian et al. Nature 2011
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Tian et al. Nature 2011
Bmi1-positive “+4 ISCs” expand when Lgr5 cells depleted
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Lineage tracing shows Bmi1 cells contribute cells to the crypt and this contribution increases when Lgr5 cells are eliminated
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Are there two ISC populations?
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How many cells can serve as stem cells in the injured tissue?
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Contribution of epithelial cells to IBD