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Yuan, X.

Publications and source records attributed to Yuan, X..

148 records · Page 9Linked to original sources

Heart enhancers with deeply conserved regulatory activity are established early in development

During the phylotypic period embryos from different genera show similar gene expression patterns, implying common regulatory mechanisms. To identify enhancers involved in the initial events of cardiogenesis, which occurs during the phylotypic period, we isolated early cardiac progenitor cells from zebrafish embryos and characterized 3838 open chromatin regions specific to this cell population. Of these regions, 162 overlapped with conserved non-coding elements (CNEs) that also mapped to open chromatin regions in human. Most of the zebrafish conserved open chromatin elements tested drove gene expression in the developing heart. Despite modest sequence identity, human orthologous open chromatin regions could recapitulate the spatial temporal expression patterns of the zebrafish sequence, potentially providing a basis for phylotypic gene expression patterns. Genome-wide, we discovered 5598 zebrafish-human conserved open chromatin regions, suggesting that a diverse repertoire of ancient enhancers is established prior to organogenesis and the phylotypic period.

genomics↗

Single-cell transcriptional regulations and accessible chromatin landscape of cell fate decisions in early heart development

Formation and segregation of the cell lineages forming the vertebrate heart have been studied extensively by genetic cell tracing techniques and by analysis of single marker gene expression both in embryos and differentiating ES cells. However, the underlying gene regulatory networks driving cell fate transitions during early cardiogenesis is only partially understood, in part due to limited cell numbers and substantial cellular heterogeneity within the early embryo. Here, we comprehensively characterized cardiac progenitor cells (CPC) marked by Nkx2-5 and Isl1 expression from embryonic days E7.5 to E9.5 using single-cell RNA sequencing. By leveraging on cell-to-cell heterogeneity, we identified different previously unknown cardiac sub-populations. Reconstruction of the developmental trajectory revealed that Isl1+ CPC represent a transitional cell population maintaining a prolonged multipotent state, whereas extended expression of Nkx-2.5 commits CPC to a unidirectional cardiomyocyte fate. Correlation-based analysis of cells in the unstable multipotent state uncovered underlying gene regulatory networks associated with differentiation. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states, which critically depend on Isl1 for accessibility of enhancers. In contrast, forced expression of Nkx2-5 eliminated multipotency of Isl1+ cells and established a unidirectional cardiomyocyte fate. Our data provides a transcriptional map for early cardiogenic events at single-cell resolution and establishes a general model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions.

developmental biology↗

Hey2 restricts cardiac progenitor addition to the developing heart

A key event in vertebrate heart development is the timely addition of second heart field (SHF) progenitor cells to the poles of the heart tube. This accretion process must occur to the proper extent to prevent a spectrum of congenital heart defects (CHDs). However, the factors that regulate this critical process are poorly understood. Here we demonstrate that Hey2, a bHLH transcriptional repressor, restricts SHF progenitor accretion to the zebrafish heart. hey2 expression demarcated a distinct domain within the cardiac progenitor population. In the absence of Hey2 function an increase in myocardial cell number and SHF progenitors was observed. We found that Hey2 limited proliferation of SHF-derived cardiomyocytes in a cell-autonomous manner, prior to heart tube formation, and further restricted the developmental window over which SHF progenitors were deployed to the heart. Taken together, our data suggests a role for Hey2 in controlling the proliferative capacity and cardiac contribution of late-differentiating cardiac progenitors.

developmental biology↗

Effect of vertical slit turbulence on metabolism and swimming behavior of juvenile grass carp (ctenopharyngodon idella)

Baffles were incorporated into the swim chamber of a flume-type swimming respirometer, and the effect of vertical slit turbulence on the swimming behavior and metabolism of juvenile grass carp were investigated. Results showed a significant lower TBF in turbulent flow than in laminar flow (p< 0.05). However, differences in TBF at different inlet velocities were not significant (p> 0.05), whether the fish passed through the baffles or not. In turbulent flow, the residence time ratios of test fish at different flow zone were low water velocity > medium velocity > high velocity. Oxygen consumption rate (MO2) increased with flow velocity and was higher in turbulent flow than in laminar flow. Further, the speed exponent c, in turbulent flow, was significantly higher than in laminar flow, indicated a decrease swimming efficiency. This study of fish swimming in turbulent flow extends knowledge of fish ecology and provides data for guiding the design of hydrokinetic turbulent where needed, so preventing ecological impacts.

animal behavior and cognition↗