Table 2.
List of studies discussing the role of regulatory signals from the Mesenchymal Component of ISC niche on ISC proliferation and differentiation
| S.No | Mesenchymal Subpopulation | ISC niche factors produced | Biological Model | Observed effects on epithelial proliferation |
|---|---|---|---|---|
| 1 | Whole stromal fraction, no subpopulation in particular111 | Wnt(s) and RSPO3 | Mice model with epithelial specific ablation Wnt signals (PorcnDel/ Villin Cre mice). | Stromal factors support epithelial proliferation and repair even in the absence of epithelial Wnts. |
| 2. | CD34+ Gp38+ αSMA_ mesenchymal cells112 |
Wnt2b, Gremlin1, RSPO1 |
SI organoids cocultured with mesenchymal cells | Stromal factors enhance Wnt-β Catenin signaling in LGR5+ ISCs supporting epithelial proliferation. |
| 3. | FoxL1+ telocytes113 | Wnt2b, Wnt4, Wnt5a | FoxL1-hDTR mice administered with diphtheria toxin, leading to ablation of telocytes. |
Reduced villus height, crypt depth; reduced stem cell proliferation (decreased Ki67 and Olfm4 expression); and reduced Wnts in subepithelial mesenchyme |
| 4. | Extracellular vesicles (EV) derived from intestinal fibroblasts114 | Amphiregulin (EGFR ligand) | Mice Small Intestinal and human colonic organoids treated with fibroblast-derived EVs | Treatment of organoids rescued them from the absence of EGF in the culture medium. The resultant increase in proliferation was seen to be mediated by EV-bound Amphiregulin, via activation of Wnt signaling in the ISC niche |
| 5. | Gli1+ and ACTA2+ mesenchymal cells115 | Wnt2b | Villin/WlscKO mice (with epithelium-specific knockout of Wingless) and intestinal organoids grown from crypts of these mice. | The knockout mice died within 14 days of the induction of mutation and showed altered villus morphology, absence of crypts in SI, and reduced expression of transcripts regulated by Wnt-β catenin signaling. Such mice and organoids were rescued by the supply of exogenous mesenchymal Wnt2b. |
RSPO1, R-spondin 1; α-SMA, α-Smooth muscle actin (α-SMA); SI, Small Intestine; FoxL1-hDTR, BAC clone of human diphtheria toxin receptor gene driven by the Foxl1 promoter; EGFR, Epidermal Growth Factor Receptor; Gli1+, Glioma-associated oncogene homolog 1; ACTA2+, Actin Alpha 2.