Airway Smooth Muscle Differentiation is Essential for Promoting Airway Size, Tracheal Cartilage Segmentation, But Dispensable for Epithelial Branching

2019 ◽  
Author(s):  
Randee E. Young ◽  
Mary-Kayt Jones ◽  
Elizabeth A. Hines ◽  
Rongbo Li ◽  
Yongfeng Luo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Differentiation ◽  
Tracheal Cartilage ◽  
Smooth Muscle Differentiation

scholarly journals Patterning the embryonic pulmonary mesenchyme

2020 ◽  
Author(s):  
Katharine Goodwin ◽  
Jacob M. Jaslove ◽  
Hirotaka Tao ◽  
Min Zhu ◽  
Sevan Hopyan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Wnt Signaling ◽  
Single Cell ◽  
Airway Smooth Muscle ◽  
Branching Morphogenesis ◽  
Muscle Differentiation ◽  
Embryonic Mouse ◽  
Mesenchymal Progenitors ◽  
Mammalian Lung ◽  
Smooth Muscle Differentiation

AbstractSmooth muscle guides morphogenesis of epithelia during development of several organs, including the mammalian lung. However, it remains unclear how airway smooth-muscle differentiation is spatiotemporally patterned and whether it originates from 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 distinct progenitors. Transcriptional variability correlates with sub-epithelial and sub-mesothelial mesenchymal compartments that are regulated by Wnt signaling. Live-imaging and tension sensors reveal patterned migratory behaviors and cortical forces in each compartment, and show that sub-epithelial mesenchyme gives rise to airway smooth muscle. Differentiation trajectory reconstruction reveals that cytoskeleton, adhesion, and Wnt signaling pathways are activated early in differentiation. Finally, we show that Wnt activation stimulates the earliest stages of differentiation and induces local accumulation of mesenchymal F-actin, which influences epithelial morphology. Our work provides the first single-cell view of pulmonary mesenchymal patterning during branching morphogenesis.

scholarly journals Smooth Muscle Differentiation Is Essential for Airway Size, Tracheal Cartilage Segmentation, but Dispensable for Epithelial Branching

2020 ◽  
Vol 53 (1) ◽  
pp. 73-85.e5 ◽  
Author(s):  
Randee E. Young ◽  
Mary-Kayt Jones ◽  
Elizabeth A. Hines ◽  
Rongbo Li ◽  
Yongfeng Luo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Differentiation ◽  
Tracheal Cartilage ◽  
Smooth Muscle Differentiation

scholarly journals Integrin-linked kinase regulates smooth muscle differentiation marker gene expression in airway tissue

2008 ◽  
Vol 295 (6) ◽  
pp. L988-L997 ◽  
Author(s):  
Yidi Wu ◽  
Youliang Huang ◽  
B. Paul Herring ◽  
Susan J. Gunst
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Airway Smooth Muscle ◽  
Muscle Differentiation ◽  
Integrin Receptors ◽  
Integrin Linked Kinase ◽  
Smooth Muscle Differentiation ◽  
Differentiation Marker

Phenotypic changes in airway smooth muscle occur with airway inflammation and asthma. These changes may be induced by alterations in the extracellular matrix that initiate signaling pathways mediated by integrin receptors. We hypothesized that integrin-linked kinase (ILK), a multidomain protein kinase that binds to the cytoplasmic tail of β-integrins, may be an important mediator of signaling pathways that regulate the growth and differentiation state of airway smooth muscle. We disrupted signaling pathways mediated by ILK in intact differentiated tracheal muscle tissues by depleting ILK protein using ILK antisense. The depletion of ILK protein increased the expression of the smooth muscle differentiation marker genes myosin heavy chain (SmMHC), SM22α, and calponin and increased the expression of SmMHC protein. Conversely, the overexpression of ILK protein reduced the mRNA levels of SmMHC, SM22α, and calponin and SmMHC protein. Analysis by chromatin immunoprecipitation showed that the binding of the transcriptional regulator serum response factor (SRF) to the promoters of SmMHC, SM22α, and calponin genes was increased in ILK-depleted tissues and decreased in tissues overexpressing ILK. ILK depletion also increased the amount of SRF that localized within the nucleus. ILK depletion and overexpression, respectively, decreased and increased the activation of its downstream substrate protein kinase B (PKB/Akt). The pharmacological inhibition of Akt activity also increased SRF binding to the promoters of smooth muscle-specific genes and increased expression of smooth muscle proteins, suggesting that ILK may exert its effects by regulating the activity of Akt. We conclude that ILK is a critical regulator of airway smooth muscle differentiation. ILK may mediate signals from integrin receptors that control airway smooth muscle differentiation in response to alterations in the extracellular matrix.

scholarly journals Malignant Melanoma with Probable Smooth Muscle Differentiation

2014 ◽  
Vol 6 (1) ◽  
pp. 16-19 ◽  
Author(s):  
Aya Morimoto ◽  
Jun Asai ◽  
Yusuke Wakabayashi ◽  
Satoshi Komori ◽  
Keiji Hanada ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Malignant Melanoma ◽  
Muscle Differentiation ◽  
Smooth Muscle Differentiation

scholarly journals Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation

2010 ◽  
Vol 79 (4-5) ◽  
pp. 244-250 ◽  
Author(s):  
Mei Cao ◽  
Gregory Tasian ◽  
Ming-Hsien Wang ◽  
Benchun Liu ◽  
Gerald Cunha ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sonic Hedgehog ◽  
Muscle Differentiation ◽  
Bladder Smooth Muscle ◽  
Smooth Muscle Differentiation
Sign in / Sign up

Export Citation Format

Share Document