Small intestine

Endocrine system

Crypt

Hormone

Enteroendocrine cell

Paneth cell

LGR5

Biology

Endocrinology

Stem cell

Cell biology

Signal transduction

Cancer stem cell

Stem cell marker

Wnt signaling pathway

Proceedings of the National Academy of Sciences

Cycling intestinal Lgr5+ stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g., Wnt, EGF) as well as surface-bound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5+ stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5 stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5+ stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.

Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion