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This article is original by Translational Medicine Network.
Please indicate the source for reprinting.
Author: Daisy Guide: Recently, a new study was published in the journal Nature Cell Biology-using stem cell organoid models to reveal a new stem cell pathway.
And it can be seen in severely injured lungs and idiopathic pulmonary fibrosis patients with COVID-19
.
The study provides a roadmap for understanding how severely damaged lungs are remodeled and provides a potential way to reverse remodeling by targeting abnormal stem cell differentiation
.
Diseases such as COVID-19 cause severe damage to the lungs, triggering the repair of abnormal stem cells, thereby changing the structure of the lungs
.
Abnormal stem cell differentiation after injury can prevent the recovery of normal lung function
.
In a collaborative study published by UCSF (University of California, San Francisco) researchers recently in the journal Nature Cell Biology, UCSF researchers Jaymin Kathiriya, Ph.
D.
and Wang Chaoqun, Ph.
D.
found that severe lung injury can trigger abnormal differentiation of lung stem cells
.
Drs.
Kathiriya and Dr.
Wang, under the guidance of Hal Chapman, MD and Tien Peng, MD, respectively, used stem cell organoid models to reveal a new stem cell pathway in the severely damaged lung and idiopathic lung fibers of COVID-19 Visible in patients with chemistry
.
Researchers published an article titled "Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5 basal cells+".
Previous studies in mice showed that mouse type 2 alveolar cells (mAEC2) are the resident stem cell population in the alveoli , They constitute the entire gas exchange surface of the lung
.
In idiopathic pulmonary fibrosis (IPF), diffuse parenchymal lung disease is the deadliest and most common form.
Human type 2 alveolar cells (hAEC2s) are lost from the alveoli, and metaplastic alveolar KRT5 basal cells appear at the same time, they usually appear In the airway
.
Strict genetic lineage tracking showed that the metaplastic KRT5 cells in the mouse alveoli were not derived from mAEC2s, but from the KRT5+−/SOX2 progenitor cells in the mouse airways after severe alveolar damage caused by fibrosis or viral infection
.
However, it is currently unclear whether there are similar populations that contribute to metaplasia of basal cells in the human airway, because the airways of these two species contain key anatomical differences
.
This is a clinically relevant issue because the alveolar KRT5 basal cells are directly related to the mortality of IPF patients
.
In this study, the researchers were surprised to find that hAEC2s (but not mAEC2s) are easily transdifferentiated into KRT5 basal cells in organoid culture and xenotransplantation
.
https:// This study provides a roadmap for understanding how severely damaged lungs are remodeled and scarred, and provides a potential way through targeting Abnormal stem cells differentiate to reverse remodeling
.
It has previously been recognized that the regenerative capacity of alveolar resident stem cells (AEC2s) works similarly in mice and humans
.
Researchers unexpectedly discovered that human AEC2s (hAEC2s) are different from mouse AEC2s, in the case of pathological fibroblasts, they can strongly transdifferentiate into functional basal cells
.
In vitro single-cell analysis of hAEC2 to basal cell trajectories revealed that there are transitional cell types and basal cell subpopulations in the lungs of patients with idiopathic pulmonary fibrosis
.
Transdifferentiation of hAEC2 into KRT5 basal cells Using a new type of fibroblast/hAEC2 organoid platform, researchers can simulate stem cell metaplasia or abnormal stem cell differentiation that occurs in severe alveolar injury
.
In addition, hAEC2s can produce findings of pathological transitional cell types and basal cells, providing experimental confirmation of stem cell trajectories seen in diseased human lungs
.
Dr.
Peng said: “We saw the differentiation of hAEC2s into basal cells for the first time.
It was so amazing that we thought it was a mistake
.
However, the rigorous verification of this new trajectory is how the lungs can be reshaped to cope with it.
Severe damage provides significant insights and provides a potential way to reverse the damage
.
"hACE2s can gradually transdifferentiate into metaplastic basal cells.
This discovery is not unique to IPF
.
Alveolar metaplastic basal cells are also common in lung slices of scleroderma and new coronary pneumonia.
In the active remodeling zone, these cells are mixed with transitional cells
.
Transitional cells are commonly found in the histological analysis of hAEC2-derived organoids, hAEC2 xenotransplantation and fibrotic lung, indicating that hAEC2s is the main source of metaplastic basal cells in severe alveolar injury diseases
.
This research lays the foundation for future research to determine the therapeutic targets that may prevent or reverse metaplastic differentiation in severe lung injury, and whether other components of the fibrotic niche, such as endothelial cells and immune cells, can drive the metaplastic phenotype
.
Reference materials: https://medicalxpress.
com/news/2021-12-uncovers-unique-stem-cell-trajectory.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital for treatment
.
Popular·Article Basic Research [Science Sub-Journal] Transforming artificial lungs-lizards provide amazing methods! Intestinal flora [Nature] Did you take hypoglycemic drugs ineffective? Because the intestinal microflora is in the process of cancer treatment [PNAS] Chinese medicinal materials thyme and oregano have found anti-cancer compounds for disease diagnosis and treatment [Nature Sub-Journal] This is another step towards changing the US$70 billion global diagnostic industry! Protein biosensors can measure toxic drugs for cardiovascular disease in cancer, arthritis, and organ transplant patients [JAMA Sub-Journal] Are you stressed? Stress increases the risk of cardiovascular disease! Scientific research [Cell Sub-Journal] Why do pain and anxiety speed up the breathing rate? The scientific research "Science" announced the breakthrough of 2021: A problem that has troubled biologists for 50 years was solved by AI and realized the dream of a Nobel Prize winner!
Please indicate the source for reprinting.
Author: Daisy Guide: Recently, a new study was published in the journal Nature Cell Biology-using stem cell organoid models to reveal a new stem cell pathway.
And it can be seen in severely injured lungs and idiopathic pulmonary fibrosis patients with COVID-19
.
The study provides a roadmap for understanding how severely damaged lungs are remodeled and provides a potential way to reverse remodeling by targeting abnormal stem cell differentiation
.
Diseases such as COVID-19 cause severe damage to the lungs, triggering the repair of abnormal stem cells, thereby changing the structure of the lungs
.
Abnormal stem cell differentiation after injury can prevent the recovery of normal lung function
.
In a collaborative study published by UCSF (University of California, San Francisco) researchers recently in the journal Nature Cell Biology, UCSF researchers Jaymin Kathiriya, Ph.
D.
and Wang Chaoqun, Ph.
D.
found that severe lung injury can trigger abnormal differentiation of lung stem cells
.
Drs.
Kathiriya and Dr.
Wang, under the guidance of Hal Chapman, MD and Tien Peng, MD, respectively, used stem cell organoid models to reveal a new stem cell pathway in the severely damaged lung and idiopathic lung fibers of COVID-19 Visible in patients with chemistry
.
Researchers published an article titled "Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5 basal cells+".
Previous studies in mice showed that mouse type 2 alveolar cells (mAEC2) are the resident stem cell population in the alveoli , They constitute the entire gas exchange surface of the lung
.
In idiopathic pulmonary fibrosis (IPF), diffuse parenchymal lung disease is the deadliest and most common form.
Human type 2 alveolar cells (hAEC2s) are lost from the alveoli, and metaplastic alveolar KRT5 basal cells appear at the same time, they usually appear In the airway
.
Strict genetic lineage tracking showed that the metaplastic KRT5 cells in the mouse alveoli were not derived from mAEC2s, but from the KRT5+−/SOX2 progenitor cells in the mouse airways after severe alveolar damage caused by fibrosis or viral infection
.
However, it is currently unclear whether there are similar populations that contribute to metaplasia of basal cells in the human airway, because the airways of these two species contain key anatomical differences
.
This is a clinically relevant issue because the alveolar KRT5 basal cells are directly related to the mortality of IPF patients
.
In this study, the researchers were surprised to find that hAEC2s (but not mAEC2s) are easily transdifferentiated into KRT5 basal cells in organoid culture and xenotransplantation
.
https:// This study provides a roadmap for understanding how severely damaged lungs are remodeled and scarred, and provides a potential way through targeting Abnormal stem cells differentiate to reverse remodeling
.
It has previously been recognized that the regenerative capacity of alveolar resident stem cells (AEC2s) works similarly in mice and humans
.
Researchers unexpectedly discovered that human AEC2s (hAEC2s) are different from mouse AEC2s, in the case of pathological fibroblasts, they can strongly transdifferentiate into functional basal cells
.
In vitro single-cell analysis of hAEC2 to basal cell trajectories revealed that there are transitional cell types and basal cell subpopulations in the lungs of patients with idiopathic pulmonary fibrosis
.
Transdifferentiation of hAEC2 into KRT5 basal cells Using a new type of fibroblast/hAEC2 organoid platform, researchers can simulate stem cell metaplasia or abnormal stem cell differentiation that occurs in severe alveolar injury
.
In addition, hAEC2s can produce findings of pathological transitional cell types and basal cells, providing experimental confirmation of stem cell trajectories seen in diseased human lungs
.
Dr.
Peng said: “We saw the differentiation of hAEC2s into basal cells for the first time.
It was so amazing that we thought it was a mistake
.
However, the rigorous verification of this new trajectory is how the lungs can be reshaped to cope with it.
Severe damage provides significant insights and provides a potential way to reverse the damage
.
"hACE2s can gradually transdifferentiate into metaplastic basal cells.
This discovery is not unique to IPF
.
Alveolar metaplastic basal cells are also common in lung slices of scleroderma and new coronary pneumonia.
In the active remodeling zone, these cells are mixed with transitional cells
.
Transitional cells are commonly found in the histological analysis of hAEC2-derived organoids, hAEC2 xenotransplantation and fibrotic lung, indicating that hAEC2s is the main source of metaplastic basal cells in severe alveolar injury diseases
.
This research lays the foundation for future research to determine the therapeutic targets that may prevent or reverse metaplastic differentiation in severe lung injury, and whether other components of the fibrotic niche, such as endothelial cells and immune cells, can drive the metaplastic phenotype
.
Reference materials: https://medicalxpress.
com/news/2021-12-uncovers-unique-stem-cell-trajectory.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital for treatment
.
Popular·Article Basic Research [Science Sub-Journal] Transforming artificial lungs-lizards provide amazing methods! Intestinal flora [Nature] Did you take hypoglycemic drugs ineffective? Because the intestinal microflora is in the process of cancer treatment [PNAS] Chinese medicinal materials thyme and oregano have found anti-cancer compounds for disease diagnosis and treatment [Nature Sub-Journal] This is another step towards changing the US$70 billion global diagnostic industry! Protein biosensors can measure toxic drugs for cardiovascular disease in cancer, arthritis, and organ transplant patients [JAMA Sub-Journal] Are you stressed? Stress increases the risk of cardiovascular disease! Scientific research [Cell Sub-Journal] Why do pain and anxiety speed up the breathing rate? The scientific research "Science" announced the breakthrough of 2021: A problem that has troubled biologists for 50 years was solved by AI and realized the dream of a Nobel Prize winner!
