PMC:5003481 / 9566-14471 JSONTXT

{"project":"2_test","denotations":[{"id":"27605182-20736237-69477474","span":{"begin":273,"end":275},"obj":"20736237"},{"id":"27605182-22895573-69477475","span":{"begin":358,"end":360},"obj":"22895573"},{"id":"27605182-20736237-69477476","span":{"begin":739,"end":741},"obj":"20736237"},{"id":"27605182-22050602-69477477","span":{"begin":796,"end":798},"obj":"22050602"},{"id":"27605182-22529925-69477478","span":{"begin":821,"end":823},"obj":"22529925"},{"id":"27605182-20736237-69477479","span":{"begin":1290,"end":1292},"obj":"20736237"},{"id":"27605182-22529925-69477480","span":{"begin":1311,"end":1313},"obj":"22529925"},{"id":"27605182-20736237-69477481","span":{"begin":1877,"end":1879},"obj":"20736237"},{"id":"27605182-22050602-69477482","span":{"begin":1940,"end":1942},"obj":"22050602"},{"id":"27605182-20736237-69477483","span":{"begin":3497,"end":3499},"obj":"20736237"},{"id":"27605182-20736237-69477484","span":{"begin":4581,"end":4583},"obj":"20736237"}],"text":"4. A Meta-Analysis of MicroRNA Microarrays in Cardiogenesis and Cardiac Aging\nBy using microRNA microarrays, we have recently reported both the most representative differentially expressed microRNAs during ventricular development, as well as the most abundantly expressed [14]. Most recently, using the complementary approach of deep-sequencing, Cao et al. [39] have provided similar findings in the developing heart. Interestingly, ten microRNAs were demonstrated to be abundantly expressed; miR-23b, miR-24, miR-23a, miR-375, miR-29a, miR-93, miR-21, miR-25, let-7b and miR-27b, in line with our previous findings. A meta-analyses approach of differentially expressed microRNAs during cardiogenesis comparing the developing mouse heart [14], the induced pluripotent stem cell-cardiomyogenesis [13] and the aging heart [12] reveals interesting patterns, as described below. From 55 microRNAs differentially expressed in the developing heart, 44 were found in the comparison to iPS-cardiogenesis and/or the aging heart. Since the aging heart experiments were performed in mice, only nine mmu-microRNA identities were similar, while in the human iPS-cardiomyogenesis, 35 equal hsa-microRNA identities were found. Comparison of the differentially expressed microRNAs in the developing heart [14] and aging heart [12] shows that those microRNAs with a progressive increase over time during heart development display arbitrary changes in the adult and aged heart (Figure 1), suggesting that these differentially expressed microRNAs during cardiogenesis are not overtly modified with aging. In line with these findings, only two (miR-494 and let-7a) among those nine microRNAs have been involved in cardiovascular biology, suggesting a rather subtle role in the adult cardiovascular system.\nIn contrast, comparison of the differentially expressed microRNAs in the developing heart [14] and induced pluripotent stem cells-derived cardiomyocytes [13] revealed 35 shared microRNAs, among which 17 (17/35; 48%) display similar expression profiles during heart development and iPS-cardiogenesis, while seven (7/35; 20%) display an opposite pattern. The remaining 11 microRNAs display arbitrary trends (11/35; 31%). Importantly, 12 out of 17 (70%) with parallel expression profiles have been already involved in cardiovascular biology. Overall, these data nicely illustrate that on the one hand, similar microRNA profiles are observed during cardiac ventricular development and iPS-derived cardiomyogenesis, highlighting the parallelism between the in vivo and the in vitro system. On the other hand, the fact that the majority of the identified microRNAs in cardiac ventricular and iPS-derived cardiomyogenesis display increasing expression levels with maturation and the fact that a role in cardiovascular development has been established for a large number of them highlights the relevance of microRNA microarray comparison and reinforces the notion of pivotal role for these microRNAs during cardiac development. Furthermore, the extrapolation of these approaches to the diseased heart will further reinforce the significant mean of microarray comparison and will further identify key microRNAs with pivotal roles in cardiovascular development and disease.\nFigure 1 A meta-analyses of microRNA microarrays during in the developing and aging cardiogenesis. Panel A illustrates the heatmap of the differentially expressed microRNAs during mouse ventricular development, as described by Chinchilla et al. [14]. Panel B illustrates the heatmap of the comparative analyses of the differentially expressed microRNAs in the developing and aging mouse heart. Observe that while those differentially expressed during cardiogenesis display increasing expression trends, the young and adult heart display no significant trends. In contrast, comparative analyses of the differentially expressed microRNAs in the developing heart and induced pluripotent stem cell-derived cardiomyocytes, over a maturation period ranging incipient cardiomyocytes (day zero) to 120 days after differentiation, nicely show subset of microRNAs with similar trends (i.e., let7 cluster) or opposite trends (see, for example, miR-103 and miR-106b), as illustrated in this heatmap on panel C. Panels A'. B', C' and C'' are graphical illustrations of microRNA representative expression trends as depicted in heatmaps on panels A, B and C, respectively. Panel A' displays only a small representation of the full list of microRNAS represented in heatmap of panel A. More detailed information can be found in Chinchilla et al. [14]. Panel C' represents a subset of panel C microRNAs displaying increased expression levels in both ventricular maturation and iPS-cardiomyogenesis, while panel C'' represents a microRNA subset display increasing expression levels during ventricular maturation, but decreasing expression levels in iPS-cardiomyogenesis.\n\n5"}