California: Acute lung injuries can trigger lung stem cells to undergo abnormal differentiation, a research has found.
The study is published in the ‘Journal of Nature Cell Biology’.
UCSF researcher Jaimin Kathiria, PhD, Chaokuni wang, PHD, Drs, Kathiria and Wang, supervised by Hal Chapman, MD, and Tien Peng, MD, respectively, use stem cell organoid models to uncover a novel stem cell pathway that is observed in severely injured lungs from COVID-19 and idiopathic pulmonary fibrosis patients.
This study offered a roadmap for understanding how severely injured lungs can remodel and scar and provided a potential route to reverse remodeling by targeting abnormal stem cell differentiation.
It has been previously acknowledged that the regenerative capacity of stem cells resident in the alveolus (AEC2s) operates similarly in mice and humans. The researchers unexpectedly found that human AEC2s (hAEC2s), in contrast to mouse AEC2s, robustly transdifferentiated into functional basal cells with signals from pathological fibroblasts.
Single-cell analysis of hAEC2-to-basal cell trajectories in vitro revealed the presence of transitional cell types and basal cell subsets, previously identified in lungs with idiopathic pulmonary fibrosis.ipf,
Using a novel fibroblast/hAEC2 organoid platform, the authors observed stem cell metaplasia, or abnormal stem cell differentiation, in severe alveolar injury.
Furthermore, the finding that hAEC2s can generate pathologic transitional cell types and basal cells provides experimental confirmation of a stem cell trajectory similar to that observed in diseased human lungs.
“The first time we saw hAEC2s differentiate into basal cells, it was so striking that we thought it was an error,” Peng said.
“But rigorous validation of this novel trajectory has provided enormous insight into how the lungs remodel in response to acute injury, and a possible route to reverse the damage,” Peng said.
The finding that hAEC2s undergo progressive transdifferentiation to metaplastic basal cells is not unique to IPF. Alveolar metaplastic basal cells are also common in scleroderma and covid lung sections, and have been intertwined with transitional cells in areas of active remodeling.
The general finding of transitional cells in hAEC2-derived organoids, as well as in histologic analysis of hAEC2 xenografts and fibrotic lungs, suggested that hAEC2s are a major source of metaplastic basal cells in diseases with severe alveolar injury.
The study provided the groundwork for future research to identify therapeutic targets that can inhibit or reverse metaplastic differentiation in acute lung injury, and whether other components of the fibrotic niche such as endothelial cells and immune cells show a metaplastic phenotype. able to run.
The study is published in the ‘Journal of Nature Cell Biology’.
UCSF researcher Jaimin Kathiria, PhD, Chaokuni wang, PHD, Drs, Kathiria and Wang, supervised by Hal Chapman, MD, and Tien Peng, MD, respectively, use stem cell organoid models to uncover a novel stem cell pathway that is observed in severely injured lungs from COVID-19 and idiopathic pulmonary fibrosis patients.
This study offered a roadmap for understanding how severely injured lungs can remodel and scar and provided a potential route to reverse remodeling by targeting abnormal stem cell differentiation.
It has been previously acknowledged that the regenerative capacity of stem cells resident in the alveolus (AEC2s) operates similarly in mice and humans. The researchers unexpectedly found that human AEC2s (hAEC2s), in contrast to mouse AEC2s, robustly transdifferentiated into functional basal cells with signals from pathological fibroblasts.
Single-cell analysis of hAEC2-to-basal cell trajectories in vitro revealed the presence of transitional cell types and basal cell subsets, previously identified in lungs with idiopathic pulmonary fibrosis.ipf,
Using a novel fibroblast/hAEC2 organoid platform, the authors observed stem cell metaplasia, or abnormal stem cell differentiation, in severe alveolar injury.
Furthermore, the finding that hAEC2s can generate pathologic transitional cell types and basal cells provides experimental confirmation of a stem cell trajectory similar to that observed in diseased human lungs.
“The first time we saw hAEC2s differentiate into basal cells, it was so striking that we thought it was an error,” Peng said.
“But rigorous validation of this novel trajectory has provided enormous insight into how the lungs remodel in response to acute injury, and a possible route to reverse the damage,” Peng said.
The finding that hAEC2s undergo progressive transdifferentiation to metaplastic basal cells is not unique to IPF. Alveolar metaplastic basal cells are also common in scleroderma and covid lung sections, and have been intertwined with transitional cells in areas of active remodeling.
The general finding of transitional cells in hAEC2-derived organoids, as well as in histologic analysis of hAEC2 xenografts and fibrotic lungs, suggested that hAEC2s are a major source of metaplastic basal cells in diseases with severe alveolar injury.
The study provided the groundwork for future research to identify therapeutic targets that can inhibit or reverse metaplastic differentiation in acute lung injury, and whether other components of the fibrotic niche such as endothelial cells and immune cells show a metaplastic phenotype. able to run.
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