HomeCirculation ResearchVol. 125, No. 4In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published1 Aug 2019https://doi.org/10.1161/RES.0000000000000290Circulation Research. 2019;125:367is related toMetabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart DiseaseSingle-Cell Transcriptomics Reveals Chemotaxis-Mediated Intraorgan Crosstalk During CardiogenesisTranscriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell ResolutionScRNA-Seq of the Cardiac Conduction System (p 379)Download figureDownload PowerPointSingle-cell RNA sequencing reveals novel markers of the cardiac conduction system, report Goodyer et al.The cardiac conduction system (CCS)—consisting of the sinoatrial node, atrioventricular node, bundle of His, bundle branches, and Purkinjie fibers—controls the rhythmic beating of the heart. As such, any disturbance to the CCS can cause arrhythmia or even sudden death. The small numbers of specialized cells comprising the CCS and the limited markers available for their identification, however, makes studying the CCS complicated. To address this and gain insight into CCS biology, Goodyer and colleagues harvested cells from CCS components of embryonic mouse hearts and performed single-cell RNA sequencing. Analysis of the data from 22 000 individually bar-coded cells revealed known cell types—based on established markers—and identified numerous new CCS-enriched genes. It also enabled identification of elusive CCS transitional cells, which connect the CCS to the surrounding myocardium and are implicated in several types of arrhythmia. Fluorescence in situ hybridization and immunolabelling of 3D-preserved, optically cleared heart tissue was used to validate several of the novel markers. Together, this sequencing and spatial data provide a gene expression atlas of the mouse CCS that will guide future studies into this essential electrical system, say the team.Chemotaxis-Mediated Second Heart Field Deployment (p 398)Download figureDownload PowerPointXiong et al, examine heart field progenitors at the single-cell RNA level.The developing mammalian heart originates from 2 areas of the early embryo called the first and second heart fields (FHF, SHF). Progenitor cells from these regions give rise to, largely speaking, different structures, with FHF cells ultimately forming the atria and left ventricle and SHF cells forming the right ventricle and outflow tract. A full understanding of how the FHF and SHF are regulated and interact, however, is lacking. To learn more, Xiong and colleagues isolated and performed RNA sequencing on ≈600 cells from each field (identified by marker expression) collected at 4 developmental time points. Sequence analysis revealed that FHF cells differentiated into cardiomyocytes in a gradual “wave-like” manner, say the authors, while SHF cells differentiated in a more step-wise fashion. The team also found high expression of migration factor MIF in FHF cells and MIF’s receptor, CXCR2, in SHF progenitors, suggesting FHF cells regulate SHF cell migration. Sure enough, blocking MIF-CXCR2 in cultured mouse embryos prevented SHF cell migration and normal development of right ventricular and outflow tract structures. Together, the results provide insights into both normal heart development and what may go awry in certain congenital heart malformations.Pulmonary Hypertension and Metabolic Syndrome (p 449)Download figureDownload PowerPointBy raising IL-6 levels, metabolic syndrome can worsen pulmonary hypertension, say Ranchoux et al.Pulmonary hypertension (PH) can arise from a number of causes, but chief among them is left heart disease (LHD), which itself can be the result of conditions such as diastolic dysfunction, aortic stenosis, or mitral valve disease. More than half of all patients whose PH is caused by LHD (known as group 2 PH) also have metabolic syndrome—a condition characterized by obesity with associated pathologies such as dislipidemia, type 2 diabetes, and high blood pressure. Metabolic syndrome can also be marked by elevated levels of the inflammatory cytokine IL-6, which in rats induces proliferation of pulmonary artery smooth muscle cells (PASMCs) and, consequently, PH. Ranchoux and colleagues now pull these pieces of the puzzle together showing that inducing metabolic syndrome in rats results in raised IL-6 and greatly exacerbated PH. Furthermore, they found that inhibition of IL-6 using either IL-6 antibodies or metaformin—a diabetes drug that the team showed can reduce IL-6 secretion from macrophages—could ameliorate such PH. IL-6 was also found to be raised in the lungs of PH patients and could induce proliferation of human PASMCs, suggesting not only that the observations in rats hold true for humans, but that metaformin could be studied as a potential treatment for group 2 PH treatment. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesMetabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart DiseaseBenoît Ranchoux, et al. Circulation Research. 2019;125:449-466Single-Cell Transcriptomics Reveals Chemotaxis-Mediated Intraorgan Crosstalk During CardiogenesisHaiqing Xiong, et al. Circulation Research. 2019;125:398-410Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell ResolutionWilliam R. Goodyer, et al. Circulation Research. 2019;125:379-397 August 2, 2019Vol 125, Issue 4 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000290 Originally publishedAugust 1, 2019 PDF download Advertisement
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