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Publication : Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate.

First Author  Wang Y Year  2018
Journal  Proc Natl Acad Sci U S A Volume  115
Issue  10 Pages  2407-2412
PubMed ID  29463737 Mgi Jnum  J:260595
Mgi Id  MGI:6121718 Doi  10.1073/pnas.1719474115
Citation  Wang Y, et al. (2018) Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate. Proc Natl Acad Sci U S A 115(10):2407-2412
abstractText  Pulmonary alveolar type I (AT1) cells cover more than 95% of alveolar surface and are essential for the air-blood barrier function of lungs. AT1 cells have been shown to retain developmental plasticity during alveolar regeneration. However, the development and heterogeneity of AT1 cells remain largely unknown. Here, we conducted a single-cell RNA-seq analysis to characterize postnatal AT1 cell development and identified insulin-like growth factor-binding protein 2 (Igfbp2) as a genetic marker specifically expressed in postnatal AT1 cells. The portion of AT1 cells expressing Igfbp2 increases during alveologenesis and in post pneumonectomy (PNX) newly formed alveoli. We found that the adult AT1 cell population contains both Hopx(+)Igfbp2(+) and Hopx(+)Igfbp2(-) AT1 cells, which have distinct cell fates during alveolar regeneration. Using an Igfbp2-CreER mouse model, we demonstrate that Hopx(+)Igfbp2(+) AT1 cells represent terminally differentiated AT1 cells that are not able to transdifferentiate into AT2 cells during post-PNX alveolar regeneration. Our study provides tools and insights that will guide future investigations into the molecular and cellular mechanism or mechanisms underlying AT1 cell fate during lung development and regeneration.
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