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Research Article
Demeng Chen
Sun Yat-sen University First Affiliated Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Radiation induced lung injury (RILI) is considered as one of the most common complications of thoracic radiation. Recent studies have focused on stem cells properties to obtain ideal therapeutic effects and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remain unknown.
Methods
We successfully obtain SOX9CreER, RosatdTomato and RosaDTA mice and identify Sox9-expressing cells through lineage tracing assay. Then we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9 expressing cells during lung regeneration via an online single cell RNA-seq dataset.
Results
In our study, we demonstrated Sox9-expressing cells promote regenerative of lung tissues and ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of online scRNA-seq dataset revealed an enrichment of PI3K/AKT pathway in Sox9-expressing cells during lung epithelium regeneration. Finally, AKT inhibitor Perifosine could suppress the regenerative effects of Sox9-expressing cells.
Conclusions
Taken together, our study suggests that Sox9-expressing cells may serve as a therapeutic target in the setting of lung tissue after RILI.
Keywords
radiation induced lung injury, Sox9, lineage tracing assay
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Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 03 Mar, 2021
No community comments so far
Editorial decision: Major Revision
On 14 Apr, 2021
Reviewer #3 agreed
On 03 Apr, 2021
Reviewer #2 agreed
On 01 Mar, 2021
Review #? received
Received 26 Feb, 2021
Reviewers invited
Invitations sent on 26 Feb, 2021
Reviewer #1 agreed
On 26 Feb, 2021
Review #1 received
Received 26 Feb, 2021
Editor assigned
On 24 Feb, 2021
Submission checks complete
On 24 Feb, 2021
Editor invited
On 24 Feb, 2021
First submitted
On 19 Feb, 2021
Metrics
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PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
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This preprint is under consideration at Stem Cell Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Demeng Chen
Sun Yat-sen University First Affiliated Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 03 Mar, 2021
No community comments so far
Editorial decision: Major Revision
On 14 Apr, 2021
Reviewer #3 agreed
On 03 Apr, 2021
Reviewer #2 agreed
On 01 Mar, 2021
Review #? received
Received 26 Feb, 2021
Reviewers invited
Invitations sent on 26 Feb, 2021
Reviewer #1 agreed
On 26 Feb, 2021
Review #1 received
Received 26 Feb, 2021
Editor assigned
On 24 Feb, 2021
Submission checks complete
On 24 Feb, 2021
Editor invited
On 24 Feb, 2021
First submitted
On 19 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Radiation induced lung injury (RILI) is considered as one of the most common complications of thoracic radiation. Recent studies have focused on stem cells properties to obtain ideal therapeutic effects and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remain unknown.
Methods
We successfully obtain SOX9CreER, RosatdTomato and RosaDTA mice and identify Sox9-expressing cells through lineage tracing assay. Then we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9 expressing cells during lung regeneration via an online single cell RNA-seq dataset.
Results
In our study, we demonstrated Sox9-expressing cells promote regenerative of lung tissues and ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of online scRNA-seq dataset revealed an enrichment of PI3K/AKT pathway in Sox9-expressing cells during lung epithelium regeneration. Finally, AKT inhibitor Perifosine could suppress the regenerative effects of Sox9-expressing cells.
Conclusions
Taken together, our study suggests that Sox9-expressing cells may serve as a therapeutic target in the setting of lung tissue after RILI.
Figure 1
Figure 2
Figure 3
Figure 4
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