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Table 2 The cellular origin of ISC niche signals in the mesenchymal compartment

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

Cell type

Produced signals




Foxl1+ telocytes

Wnt-act (Wnt2b, 5a, Rspo3); Wnti (Sfrp1, Dkk3); BMPi (Chrdl1, Grem 1); BMPs (BMP4, 5, 6, 7); Others (Fgf7, Hgf, Igf1, Igfbp5, Pgf, Ctgf)

As an essential source of Wnt signals for ISCs.

Ablation of Foxl1+ cells in Foxl1-hDTR or Foxl1-cre; Rosa26-iDTR mice causes abrupt cessation of ISC proliferation; Deletion of Porcn in Foxl1-creERT2 mice causes rapid decline of Wnt activity and crypt loss.

(Aoki et al., 2016; Shoshkes-Carmel et al., 2018)

Gli1+ mesenchymal cells

Wnt-act (Wnt2, 2b, and 4; Rspo3); Wnti (Sfrp1)

An essential Wnt source in colon and a reserve Wnt source in SI; Responsive to damage-induced intestinal regeneration

Deletion of Wls in Gli1-creERT2 mice causes ISC loss in colon over time; Deletion of Wls in Vilin-creERT2 and GLI1-creERT2 combined mice causes reduced ISC proliferation in SI over time; ScRNA-seq data suggests the expansion of Gli+ cells following epithelial damage.

(Degirmenci et al., 2018)

CD81+PDGFR-αlo trophocytes

BMPi (Grem1)

Sustain ISCs in vivo; promote ISC expansion in vitro.

Ablation of Grem1+ cells in Grem1–creERT2; Rosa26–iDTR mice causes rapid ISC loss; The Grem1+ trophocytes can support enteroid growth without exogenous Wnt/Rspo and BMPi factors.

(McCarthy et al., 2020)

CD34+GP38+ mesenchymal cells

Wnt-act (Wnt2b, Rspo1); BMPi (Grem1); Others (Areg, Fgf7, Fgf10, Ptgs2 and Col1a1);

Maintain ISCs in vitro; contribute to intestinal repair after injury.

CD34+Gp38+ cells promote ISC maintenance in intestinal organoids; these cells are rapidly expanded in DSS-mediated colitis.

(Stzepourginski et al., 2017)

PDGFR-α+ pericryptal stromal cells

Wnts and Rspo3

As critical source of Wnts and Rspo3 for ISC self-renewal.

Deletion of Porcn in PdgfRα-cre mice blocks crypt formation; Deletion of Rspo3 in PdgfRα-cre mice causes decreased crypt WNT/β-catenin signaling and predisposes to DSS-induced colitis.

(Greicius et al., 2018)

Cspg4+ pericyte-like

Wnt2b and Wnt4

Required for gut regeneration.

Deletion of Wls using Cspg4-cre mice causes reduced ISCs and comprised regeneration following irradiation.

(Kim et al., 2020)

CD90+ fibroblasts

BMPi (Grem1); Wnt-act (Wnt2b, and Rspo3); Others (Sema3).

Support the organoid growth.

Co-culture of CD90+ crypt fibroblasts supports organoid growth in R-spondin-reduced medium;

(Karpus et al., 2019)


Wnt-act (Rspo3); Wnti (Dkk3);


Coculture of myofibroblasts and SI crypts supports long-term growth without Rspo1.

(Lei et al., 2014)

Deletion of Porcn using Myh11-creERT2 and/or Villin-creERT2 lines all fails to disrupt crypt proliferation or Wnt pathway activity;

(San Roman et al., 2014)

Endothelial, immune, smooth muscle cells, macrophages, etc.

Wnt-act (Rspo3), Wnti, BMPi and NOTCH ligands (Dll1 and Dll4) in many of these cells

N. D

N. D.

(Bauché et al., 2018; Hansen et al., 2019; Ogasawara et al., 2018)