Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis

  title={Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis},
  author={Monica Cassandras and Chaoqun Wang and Jaymin J. Kathiriya and Tatsuya Tsukui and Peri Matatia and Michael A. Matthay and Paul J. Wolters and Ari B. Molofsky and Dean Sheppard and Hal Chapman and Tien Peng},
Organ fibrosis is often accompanied by aberrant epithelial reprogramming, culminating in a transformed barrier composed of scar and metaplastic epithelium. Understanding how the scar promotes an abnormal epithelial response could better inform strategies to reverse the fibrotic damage. Here we show that Gli1+ mesenchymal stromal cells (MSCs), previously shown to contribute to myofibroblasts in the scar, promote metaplastic differentiation of airway progenitors into KRT5+ basal cells in vitro… 

Human alveolar Type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells

It is reported that fibrotic signalling in the lung mesenchyme leads to transdifferentiation of human alveolar type 2 cells into KRT5 + basal cells, providing a mechanistic explanation for the pathology associated with severe lung injuries.



Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis.

BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors

In the mouse airway epithelium, regeneration after injury involves transient downregulation of BMP signaling to promote proliferation, followed by cell shedding to restore cell density, which reveals crucial roles for both B MP signaling and cell shedding in homeostasis of the respiratory epithelia.

Local lung hypoxia determines epithelial fate decisions during alveolar regeneration

It is shown that local lung hypoxia, through Hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5pos basal-like cell expansion and is ultimately inferior to AEC2 reconstitution in restoring normal lung function.

Lineage-negative Progenitors Mobilize to Regenerate Lung Epithelium after Major Injury

It is indicated that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.

GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells

The data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.

Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype

It is shown that differential hedgehog activation segregates mesenchymal identities of distinct fibroblast subsets and that disruption of fibro Blast identity can alter the alveolar stem cell niche, leading to emphysematous changes in the murine lung.