Cells proposed to be derived from ISCs at the crypt base
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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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Absorptive cells Enterocyte : nutrient absorption

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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


Are there two ISC populations?


How many cells can serve as stem cells in the injured tissue?


Contribution of epithelial cells to IBD


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