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Cells proposed to be derived from ISCs at the crypt base. Other Tuft cells M-cells. Absorptive cells Enterocyte : nutrient absorption. Secretory cells Goblet cell: mucus secretion Paneth cells: antimicrobial product secretion Enteroendocrine cells: hormone secretion.
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Cells proposed to be derived from ISCs at the crypt base Other Tuft cells M-cells Absorptive cells Enterocyte: nutrient absorption Secretory cells Goblet cell: mucus secretion Paneth cells: antimicrobial product secretion Enteroendocrine cells: hormone secretion
Colon similar to small intestine: Similar cell types are derived from ISCs at the crypt base
Labeling proliferating cells and following their migration: ~5 days from birth to death
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
Lgr5 expression restricted to CBC cells Lgr5 expression Marks CBCs Barker N. et al, Nature 449:1003, 2007
Use of an Lgr5-GFP-Cre transgene to mark Lgr5-expressing cells and their descendents
Use of an Lgr5-GFP-Cre transgene to mark Lgr5-expressing cells and their descendents CBC stem cells mapping below +4 1 5 60 days following Cre activation
Single Lgr5+ cells generate crypt–villus structures. T Sato et al. Nature000, 1-4 (2009) doi:10.1038/nature07935
Composition of single stem cell-derived organoids. T Sato et al. Nature000, 1-4 (2009) doi:10.1038/nature07935
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 Barker N. et al, Nature 449:1003, 2007
An Lgr5-Diptheria toxin receptor fusion gene can trigger the elimination of Lgr5-expressing cells Tian et al. Nature 2011
Crypts develop normally even when Lgr5 cells depleted Tian et al. Nature 2011
Bmi1-positive “+4 ISCs” expand when Lgr5 cells depleted Tian et al. Nature 2011
Lineage tracing shows Bmi1 cells contribute cells to the crypt and this contribution increases when Lgr5 cells are eliminated
How many cells can serve as stem cells in the injured tissue?
