Journal article

Publication year: 2017

Pages: 1566-1578

Journal: Stem Cells

Volume number: 35

Issue number: 6

ISSN: 1066-5099

eISSN: 1549-4918

Open access status: Bronze

DOI Link: https://doi.org/10.1002/stem.2615

Publisher: Oxford University Press

Abstract: 
ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown. Using Fgf10(CreERT2), Wt1(CreERT2), Gli1(CreERT2), and Axin2(CreERT2) inducible driver lines in combination with a tdTomato(flox) reporter line, the respective differentiation of each pool of labeled progenitor cells along the SMC and alveolar MYF lineages was quantified. The results revealed that while FGF10(+) and WT1(+) cells show a minor contribution to the SMC lineage, GLI1(+) and AXIN2(+) cells significantly contribute to both the SMC and alveolar MYF lineages, but with limited specificity. Lineage tracing using the Acta2-CreERT2 transgenic line showed that ACTA2(+) cells labeled at embryonic day (E)11.5 do not expand significantly to give rise to new SMCs at E18.5. However, ACTA2(+) cells labeled at E15.5 give rise to the majority (85%-97%) of the SMCs in the lung at E18.5 as well as alveolar MYF progenitors in the lung parenchyma. Fluorescence-activated cell sorting-based isolation of different subpopulations of ACTA2(+) lineage-traced cells followed by gene arrays, identified transcriptomic signatures for alveolar MYF progenitors versus airway and vascular SMCs at E18.5. Our results establish a new transcriptional landscape for further experiments addressing the function of signaling pathways in the formation of different subpopulations of ACTA2(+) cells.

Harvard Citation style: Moiseenko, A., Kheirollahi, V., Chao, C., Ahmadvand, N., Quantius, J., Wilhelm, J., et al. (2017) Origin and Characterization of Alpha Smooth Muscle Actin-Positive Cells During Murine Lung Development, Stem Cells, 35(6), pp. 1566-1578. https://doi.org/10.1002/stem.2615

APA Citation style: Moiseenko, A., Kheirollahi, V., Chao, C., Ahmadvand, N., Quantius, J., Wilhelm, J., Herold, S., Ahlbrecht, K., Morty, R., Rizvanov, A., Minoo, P., El Agha, E., & Bellusci, S. (2017). Origin and Characterization of Alpha Smooth Muscle Actin-Positive Cells During Murine Lung Development. Stem Cells. 35(6), 1566-1578. https://doi.org/10.1002/stem.2615