| First Author | Zhang K | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 7252 |
| PubMed ID | 36433959 | Mgi Jnum | J:332095 |
| Mgi Id | MGI:7410215 | Doi | 10.1038/s41467-022-34763-y |
| Citation | Zhang K, et al. (2022) mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity. Nat Commun 13(1):7252 |
| abstractText | 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 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. |
