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

From: The cellular niche for intestinal stem cells: a team effort

Region Cell type Produced signals Function Methods Ref.
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 Reg4DTR-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)