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| Status |
Public on Nov 03, 2022 |
| Title |
mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Formation of branched organs requires sequential differentiation of stem cells. In this work, we find that the conducting airways derived from SOX2+ progenitors in the murine lungs fail to form without mTOR complex 1 (mTORC1) signaling and are replaced by lung cysts. Proximal-distal patterning through transitioning of distal SOX9+ progenitors to the proximal SOX2+ cells is disrupted. Mitochondria number and ATP production are reduced. Compromised mitochondrial capacity results in a similar defect as that in mTORC1-deficient lungs. This suggests that mTORC1 promotes differentiation of SOX9+ progenitors to form the conducting airways by modulating mitochondrial capacity. Surprisingly, in all mutants saccules are produced from lung cysts at the proper developmental time despite defective branching. SOX9+ progenitors also differentiate into alveolar epithelial type I and type II cells within saccules. These findings highlight selective utilization of energy and regulatory programs during stem cell differentiation to produce distinct structures of the mammalian lungs.
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| Overall design |
Examine the difference of gene expression among Rptor-, Tfam-, Cox10-deficient and their littermate control lungs
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| Contributor(s) |
Zhang K, Yao E, Chuang E, Chen B, Chuang EY, Chuang P |
| Citation(s) |
36433959 |
| |
| Submission date |
Sep 12, 2022 |
| Last update date |
Dec 15, 2022 |
| Contact name |
Pao-Tien Chuang |
| Organization name |
University of California, San Francisco
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| Street address |
555 Mission Bay Blvd. South
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| City |
San Francisco |
| ZIP/Postal code |
CA 94158-3118 |
| Country |
USA |
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| Platforms (1) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA879749 |
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