Functionally Conserved Noncoding Regulators of Cardiomyocyte Proliferation and Regeneration in Mouse and Human

• DOI: 10.1161/circgen.117.001805
• Publication Date: 2018-10-09T08:03:34Z
• Authors: Martyna Adamowicz; Claire C. Morgan; Bernhard J. Haubner; Michela Noseda; Melissa J. Collins; Marta Abreu Paiva; Prashant K. Sriva...; Pascal Gellert; Bonnie Razzaghi; Peter O’Gara; Priyanka Raina; Laurence Game; Leonardo Bottolo; Michael D. Schneider; Sian E. Harding; Josef Penninger; Timothy J. Aitman
• Keywords: Heart development

Background: The adult mammalian heart has little regenerative capacity after myocardial infarction (MI), whereas neonatal mouse regenerates without scarring or dysfunction. However, the underlying pathways are poorly defined. We sought to derive insights into regulating development of and cardiac regeneration post-MI. Methods Results: Total RNA-seq through first 10 days postnatal life (referred as P3, P5, P10) revealed a previously unobserved transition in microRNA (miRNA) expression between P3 P5 associated specifically with altered protein-coding genes on focal adhesion pathway cessation cardiomyocyte cell division. found profound changes coding noncoding transcriptome MI, evidence essentially complete healing by P10. Over two-thirds each messenger RNAs, long miRNAs that were differentially expressed post-MI during normal development, suggesting common regulatory for regeneration. selected exemplars implicated our data set regulators proliferation. Several these showed functional influence In addition, subset miRNAs, miR-144-3p, miR-195a-5p, miR-451a, miR-6240 conservation human cardiomyocytes. Conclusions: sets RNAs we report here merit further investigation gatekeepers division targets extension period beyond period.