Table 1 The cellular orign of niche signals in the epithelial compartment

Small intestine

Paneth cells

Wnt3;

Notch ligand (Dll4);

Growth factors (TGFα and EGF);

Promoting ISC self-renewal

The isolated Paneth cells can replace Wnt3 to support intestinal organoid growth in 3D cultures;

(Sato et al., 2011)

Mixed results about the requirement for ISC maintenance in vivo.

(Bastide et al., 2007; Durand et al., 2012; Emily M. Garabedian, 1997; Kim et al., 2012; Mori-Akiyama et al., 2007; Sato et al., 2011; van Es et al., 2019)

Enteroendocrine cells (facultative)

Dll1

Can replace the vacated positions following Paneth cell ablation to support ISC maintenance.

Following the ablation of Paneth cells in Lyz1-DTR mice, EEs and tuft cells can repopulate the vacancies and provide Notch ligands for maintaining ISCs.

(van Es et al., 2019)

Tuft cells (facultative)

Dll1

Same as above.

Same as above

(van Es et al., 2019)

Large intestine

Reg4⁺ deep secretory cells (DSCs)

Dll1 and Dll4; EGF

Maintenance of colonic ISCs

Ablation of DSCs in Reg4^DTR-Red/+ mice causes ISC loss; Coculturing of ISCs with Reg4⁺ DSCs support organoid formation from single ISCs.

(Rothenberg et al., 2012; Sasaki et al., 2016)