Cells proposed to be derived from ISCs at the crypt base
Absorptive cells
Enterocyte: nutrient absorption
Secretory cells
Goblet cell: mucus secretion
Paneth cells: antimicrobial product secretion
Enteroendocrine cells: hormone secretion
Other
Tuft cells
M-cells
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. Nature 000, 1-4 (2009) doi:10.1038/nature07935
Composition of single stem cell-derived organoids.
T Sato et al. Nature 000, 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