Patterning the embryonic pulmonary mesenchyme.

TitlePatterning the embryonic pulmonary mesenchyme.
Publication TypeJournal Article
Year of Publication2022
AuthorsGoodwin, K, Jaslove, JM, Tao, H, Zhu, M, Hopyan, S, Nelson, CM
JournaliScience
Volume25
Issue3
Pagination103838
Date Published2022 Mar 18
ISSN2589-0042
Abstract

<p>Smooth muscle guides the morphogenesis of several epithelia during organogenesis, including the mammalian airways. However, it remains unclear how airway smooth muscle differentiation is spatiotemporally patterned and whether it originates from transcriptionally distinct mesenchymal progenitors. Using single-cell RNA-sequencing of embryonic mouse lungs, we show that the pulmonary mesenchyme contains a continuum of cell identities, but no transcriptionally distinct progenitors. Transcriptional variability correlates with spatially distinct sub-epithelial and sub-mesothelial mesenchymal compartments that are regulated by Wnt signaling. Live-imaging and tension-sensors reveal compartment-specific migratory behaviors and cortical forces and show that sub-epithelial mesenchyme contributes to airway smooth muscle. Reconstructing differentiation trajectories reveals early activation of cytoskeletal and Wnt signaling genes. Consistently, Wnt activation induces the earliest stages of smooth muscle differentiation and local accumulation of mesenchymal F-actin, which influences epithelial morphology. Our single-cell approach uncovers the principles of pulmonary mesenchymal patterning and identifies a morphogenetically active mesenchymal layer that sculpts the airway epithelium.</p>

DOI10.1016/j.isci.2022.103838
Alternate JournaliScience
PubMed ID35252804
PubMed Central IDPMC8889149
Grant ListF30 HL139039 / HL / NHLBI NIH HHS / United States
R01 HD099030 / HD / NICHD NIH HHS / United States