{"id":387805,"date":"2021-12-30T23:22:37","date_gmt":"2021-12-30T20:22:37","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/study-uncovers-unique-stem-cell-trajectory-in-lungs-damaged-by-covid-19-and-pulmonary-fibrosis\/"},"modified":"2021-12-30T23:22:37","modified_gmt":"2021-12-30T20:22:37","slug":"study-uncovers-unique-stem-cell-trajectory-in-lungs-damaged-by-covid-19-and-pulmonary-fibrosis","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/study-uncovers-unique-stem-cell-trajectory-in-lungs-damaged-by-covid-19-and-pulmonary-fibrosis\/","title":{"rendered":"#Study uncovers unique stem cell trajectory in lungs damaged by COVID-19 and pulmonary fibrosis"},"content":{"rendered":"

“#Study uncovers unique stem cell trajectory in lungs damaged by COVID-19 and pulmonary fibrosis<\/strong>”<\/p>\n

\n
\n
\n
\n \"cell\"
\n Credit: Unsplash\/CC0 Public Domain
\n <\/figcaption><\/figure>\n<\/p><\/div>\n<\/div>\n

Severe injuries to the lung from diseases such as COVID-19 trigger abnormal stem cell repair\u00a0that alters the\u00a0architecture of the lung. The\u00a0aberrant stem cell differentiation in response to injury\u00a0can prevent the restoration of normal lung function.\u00a0\u00a0\n <\/p>\n

In\u00a0a\u00a0collaborative study between\u00a0UCSF\u00a0researchers\u00a0app<\/a>earing\u00a0December 30\u00a0in\u00a0Nature Cell Biology<\/i>,\u00a0UCSF researchers\u00a0Jaymin\u00a0Kathiriya, Ph.D., and\u00a0Chaoqun\u00a0Wang, Ph.D.,\u00a0discovered that severe lung injuries can trigger lung stem cells to undergo abnormal differentiation.\u00a0Drs.\u00a0Kathiriya\u00a0and Wang,\u00a0supervised by\u00a0Hal Chapman, MD, and\u00a0Tien Peng, MD,\u00a0respectively,\u00a0utilized stem cell organoid models to uncover a novel stem cell pathway that is seen in severely injured lungs from COVID-19 and idiopathic pulmonary fibrosis patients.\u00a0\u00a0<\/p>\n

This\u00a0study\u00a0offers a roadmap to understand how severely injured lungs can remodel and scar and provides a potential pathway to reverse the remodeling by targeting the abnormal stem cells differentiation.\u202f\u00a0<\/p>\n

It has been previously accepted\u00a0that the regenerative capacity of resident stem cells\u00a0of the alveolus\u00a0(AEC2s),\u00a0operates similarly\u00a0mice\u00a0and humans.\u00a0The researchers unexpectedly\u00a0found that human\u00a0AEC2s\u00a0(hAEC2s), unlike mouse AEC2s,\u00a0robustly transdifferentiate into functional basal cells with cues from pathological\u00a0fibroblasts.\u00a0Single-cell analysis of the hAEC2-to-basal cell trajectory in vitro revealed the presence of\u00a0transitional\u00a0cell types and basal cell subsets previously identified in\u00a0lungs with Idiopathic Pulmonary Fibrosis (IPF).\u00a0\u00a0<\/p>\n

Utilizing a\u00a0novel\u00a0fibroblast\/hAEC2 organoid\u00a0platform, the authors could model\u00a0the\u00a0stem cell metaplasia, or abnormal\u00a0stem cell differentiation,\u00a0seen in severe alveolar\u00a0injury.\u00a0Furthermore, the discovery that hAEC2s can generate pathologic transitional cell types and basal cells provides experimental confirmation of a stem cell trajectory that is seen in\u00a0diseased human lungs.\u00a0<\/p>\n

“The first time we saw hAEC2s differentiating into basal cells, it was so striking that we thought it was an error,” said Peng.\u00a0“But rigorous validation of this novel trajectory has provided enormous insight on how the lung remodels in response to severe injury, and a potential path to reverse the damage.”\u00a0<\/p>\n

The finding that\u00a0hAEC2s undergo progressive transdifferentiation to metaplastic basal cells is not unique to IPF. Alveolar metaplastic basal cells are also common in sections of scleroderma and COVID lungs, and these are intermingled with\u00a0transitional cells\u00a0in areas of active remodeling.\u00a0The common finding of\u00a0transitional cells\u00a0in hAEC2-derived organoids as well as hAEC2 xenografts and in histologic analyses of fibrotic lungs,\u00a0suggest hAEC2s are a major source of metaplastic basal cells in diseases with severe alveolar injury.\u00a0\u00a0<\/p>\n

The study provides the groundwork for future research\u00a0to\u00a0identify\u00a0therapeutic targets\u00a0that might prevent or reverse metaplastic differentiation in severe lung injury,\u00a0and whether other components of the fibrotic niche such as endothelial cells and immune cells are able to drive the metaplastic phenotype.\u00a0\n <\/p>\n\n

\n

Study reveals new mechanism of lung tissue regeneration\n <\/p><\/div>\n

\n
\n More information:<\/strong>
\n Jaymin J. Kathiriya et al, Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells, Nature Cell Biology<\/i> (2021). DOI: 10.1038\/s41556-021-00809-4<\/a><\/p><\/div>\n

\n Provided by
\n University of California San Francisco Medical Center<\/p>\n

<\/p>\n

\n

Citation<\/strong>:
\n Study uncovers unique stem cell trajectory in lungs damaged by COVID-19 and pulmonary fibrosis (2021, December 30)
\n retrieved 30 December 2021
\n from https:\/\/medicalxpress.com\/news<\/a>\/2021-12-uncovers-unique-stem-cell-trajectory.html<\/p>\n

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
\n part may be reproduced without the written permission. The content is provided for information purposes only.<\/p><\/div>\n<\/p><\/div>\n