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Finding the niche for colonic stem cells
Degirmenci B, Valenta T, Dimitrieva S, et al. GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature 2018;558:449–453.
The intestinal stem cell niche is a collection of cells that supports the maintenance and self-renewal of stem cells. The Wnt signalling pathway is crucial for this process and Paneth cells residing at the crypt base provide Wnt ligands. Paneth cell loss though does not affect intestinal homeostasis and colonic crypts lack Paneth cells. This paper studies the role of Gli1+ mesenchymal cells surrounding crypts as niche components. Lineage tracing studies showed that Gli1+ cells are long-lived and act as progenitors, giving rise to differentiated mesenchymal cell types in vitro. Blocking Wnt secretion in Gli1+ cells in vivo led to crypt loss and intestinal breakdown at 21 days, accompanied by reduction in epithelial Wnt targets. Addition of exogenous Wnt delayed crypt loss. In the small bowel, blocking Wnt in both epithelial cells and Gli1+ cells produced the same effect. Epithelial cell Wnt blockade alone led to an expanded Gli1+ population to compensate. When Gli1+ cells were co-cultured with colonic organoids, they could maintain growth without the addition of exogenous Wnt, giving further evidence that these were niche cells. Sequencing of Gli1+ cells revealed a diverse population with eight clusters. In vitro Gli1+ cells were responsive to Hedgehog stimulation and when Wnt was blocked, Hedgehog signalling increased to augment Gli1+ cells. In summary, Gli1+ cells provide Wnt signals and act as the niche for colonic stem cells, and the reserve niche for small intestinal stem cells.
Integrated multi-omics of the faecal microbiome and host identifies interactions relevant to the development of hepatic steatosis
Hoyles L, Fernández-Real J-M, Federici M, et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat Med 2018;24:1070–1080.
Alterations in the microbiome have been associated with numerous diseases. However, the interaction between the microbiota and host in …
Contributors Dr Sujata Biswas, Dr Prakash Ramachandran, Dr Francesca Moroni, Prof Raja Atreya, Dr John Leeds, Dr Mairi McLean.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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