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Publication : Genomic, epigenomic, and biophysical cues controlling the emergence of the lung alveolus.

First Author  Zepp JA Year  2021
Journal  Science Volume  371
Issue  6534 PubMed ID  33707239
Mgi Jnum  J:303269 Mgi Id  MGI:6512988
Doi  10.1126/science.abc3172 Citation  Zepp JA, et al. (2021) Genomic, epigenomic, and biophysical cues controlling the emergence of the lung alveolus. Science 371(6534)
abstractText  The lung alveolus is the functional unit of the respiratory system required for gas exchange. During the transition to air breathing at birth, biophysical forces are thought to shape the emerging tissue niche. However, the intercellular signaling that drives these processes remains poorly understood. Applying a multimodal approach, we identified alveolar type 1 (AT1) epithelial cells as a distinct signaling hub. Lineage tracing demonstrates that AT1 progenitors align with receptive, force-exerting myofibroblasts in a spatial and temporal manner. Through single-cell chromatin accessibility and pathway expression (SCAPE) analysis, we demonstrate that AT1-restricted ligands are required for myofibroblasts and alveolar formation. These studies show that the alignment of cell fates, mediated by biophysical and AT1-derived paracrine signals, drives the extensive tissue remodeling required for postnatal respiration.
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