Genomic stability of pulmonary artery endothelial colony-forming cells in culture

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Cleveland Clinic Foundation

Details

Original languageEnglish (US)
Pages (from-to)421-427
Number of pages7
JournalPulmonary Circulation
Volume7
Issue number2
StatusPublished - Jan 1 2017
Peer-reviewedYes

Abstract

Pulmonary vascular remodeling, including proliferation and migration of pulmonary artery endothelial cells (PAEC), is a pathologic hallmark of pulmonary arterial hypertension (PAH). Multiple studies have shown evidence of increased levels of DNA damage and lineage-specific genetic changes in PAH lung vascular cells, suggesting increased genomic instability. Highly proliferative endothelial colony-forming cell (ECFC) clones can be isolated from PAEC. Here we utilized ECFC to track chromosomal copy number of 20 PAH and eight control clones across serial passages using genome-wide microarrays. All PAH clones were genomically stable for at least 20–22 population doublings. At very late passages, ECFC developed a highly aneuploid karyotype, but this was generally associated with senescence and was common to both PAH and controls. We also utilized ECFC to isolate the chromosomally abnormal cells from a mixed population of PAH PAEC. Analysis of PAEC harboring two different changes affecting chromosomes 1 and X demonstrated that both abnormalities were present in the same clone, indicating they originated in a common ancestral cell. In a second case, with a partial duplication of chromosome 17, clones carrying the duplication were more frequent at later passages than chromosomally normal clones from the same PAEC culture, suggesting the rearrangement may confer a proliferative advantage. Overall, this small study suggests that endothelial cells from PAH lungs are stable in culture, but that when chromosome abnormalities do occur, they may confer a selective advantage that allows expansion of the abnormal cell population and could contribute to lung vascular remodeling in vivo.

    Research areas

  • Endothelial cells, Genomic stability, Karyotype, Pulmonary hypertension

Citation formats

APA

Drake, K. M., Federici, C., Duong, H. T., Comhair, S. A., Erzurum, S. C., Asosingh, K., & Aldred, M. A. (2017). Genomic stability of pulmonary artery endothelial colony-forming cells in culture. Pulmonary Circulation, 7(2), 421-427. https://doi.org/10.1177/2045893217700901

Harvard

Drake, KM, Federici, C, Duong, HT, Comhair, SA, Erzurum, SC, Asosingh, K & Aldred, MA 2017, 'Genomic stability of pulmonary artery endothelial colony-forming cells in culture', Pulmonary Circulation, vol. 7, no. 2, pp. 421-427. https://doi.org/10.1177/2045893217700901