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Publication : Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex.

First Author  Bressan M Year  2018
Journal  Cell Rep Volume  23
Issue  8 Pages  2283-2291
PubMed ID  29791840 Mgi Jnum  J:271989
Mgi Id  MGI:6280097 Doi  10.1016/j.celrep.2018.04.075
Citation  Bressan M, et al. (2018) Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex. Cell Rep 23(8):2283-2291
abstractText  Impulses generated by a multicellular, bioelectric signaling center termed the sinoatrial node (SAN) stimulate the rhythmic contraction of the heart. The SAN consists of a network of electrochemically oscillating pacemaker cells encased in a heterogeneous connective tissue microenvironment. Although the cellular composition of the SAN has been a point of interest for more than a century, the biological processes that drive the tissue-level assembly of the cells within the SAN are unknown. Here, we demonstrate that the SAN's structural features result from a developmental process during which mesenchymal cells derived from a multipotent progenitor structure, the proepicardium, integrate with and surround pacemaker myocardium. This process actively remodels the forming SAN and is necessary for sustained electrogenic signal generation and propagation. Collectively, these findings provide experimental evidence for how the microenvironmental architecture of the SAN is patterned and demonstrate that proper cellular arrangement is critical for cardiac pacemaker biorhythmicity.
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