Covid-19, unique stem cell trajectory damage to the lungs by pulmonary fibrosis: study


California: Research has found that severe lung injuries can trigger lung stem cells to undergo abnormal differentiation.
The study is published in the journal Nature Cell Biology.
UCSF researchers Jaimeen Kathiria, PhD, Chaokun Wang, PhD, Dr.. Kathiria And was overseen by Wang Currently Chapman, MD, and TN Peng, MD, used stem cell organoid models to uncover novel novel stem cell pathways found in severely injured lungs of covid-19 and idiopathic pulmonary fibrosis patients, respectively.
This study offers a roadmap for understanding how severely injured lungs can remodel and scar and provides a potential way to reverse remodeling by targeting abnormal stem cell differentiation.
It has previously been suggested that the regenerative capacity of resident stem cells of alveoli (AEC2s) administered equally in mice and humans. Researchers unexpectedly found that human AEC2s (hAEC2s), unlike mouse AEC2s, strongly alter functional stem cells with signals of pathological fibroblasts.
Single-cell analysis of hAEC2-to-basal cell trajectory in vitro revealed the presence of previously identified transitional cell types and basal cell subsets in the lung with idiopathic pulmonary fibrosis ().IPF).
Using the novel Fibroblast / hAEC2 organoid platform, authors can model stem cell metaplasia or abnormal stem cell differentiation, found in severe alveolar trauma.
Furthermore, the discovery that hAEC2 can produce pathologically transitional cell types and stem cells provides experimental confirmation of stem cell trajectories found in diseased human lungs.
“The first time we saw a differentiation of hAEC2 into stem cells, it was so amazing that we thought it was a mistake,” Peng said.
“But the rigid recognition of this novel pathway has provided tremendous insights into how the lungs regenerate in response to a serious injury and the potential pathway for reversing the damage,” Peng added.
The discovery that HAEC2 undergoes progressive transdeferentiation in metaplastic basal cells is not unique to IPF. Alveolar metaplastic basal cells are also common in scleroderma and covid lung sections, and merge with infected cells in areas of active remodeling.
General detection of transitional cells in hAEC2-derived organoids as well as histologic analysis of hAEC2 xenografts and fibrotic lungs, suggests that hAEC2 is a major source of metaplastic basal cells in diseases with severe alveolar injury.
This study has provided the basis for future research to identify therapeutic targets that may inhibit or reverse metaplastic differentiation in severe lung injury, and whether other components of the fibrotic structure such as endothelial cells and immune cells metaplast Kemotapam for chemoplasm.

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