Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing

Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed the gene expression profiles of specialized tissue-resident EC subtypes that are capable of clonal expansion and contribute to adult angiogenesis, a process of new vessel formation from the pre-existing vasculature. These specialized tissue-resident ECs have been identified in various different mouse tissues, including aortic endothelium, liver, heart, lung, skin, skeletal muscle, retina, choroid, and brain. Transcription factors and signaling pathways have also been identified in the specialized tissue-resident ECs that control angiogenesis. Furthermore, scRNA-seq has also documented responses of ECs in diseases such as cancer, age-related macular degeneration, Alzheimer’s disease, atherosclerosis, and myocardial infarction. These new findings revealed by scRNA-seq have the potential to provide new therapeutic targets for different diseases associated with blood vessels. In this article, we summarize recent advances in the understanding of the vascular endothelial cell heterogeneity and endothelial stem cells associated with angiogenesis and homeostasis in mice and humans, and we discuss future prospects for the application of scRNA-seq technology

Cellular Heterogeneity and Stem Cells of Vascular Endothelial Cells in Blood Vessel Formation and Homeostasis: Insights from single-cell RNA Sequencing

Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed the gene expression profiles of specialized tissue-resident EC subtypes that are capable of clonal expansion and contribute to adult angiogenesis, a process of new vessel formation from the pre-existing vasculature. These specialized tissue-resident ECs have been identified in various different mouse tissues, including aortic endothelium, liver, heart, lung, skin, skeletal muscle, retina, choroid, and brain. Transcription factors and signaling pathways have also been identified in the specialized tissue-resident ECs that control angiogenesis. Furthermore, scRNA-seq has also documented responses of ECs in diseases such as cancer, age-related macular degeneration, Alzheimer\u27s disease, atherosclerosis, and myocardial infarction. These new findings revealed by scRNA-seq have the potential to provide new therapeutic targets for different diseases associated with blood vessels. In this article, we summarize recent advances in the understanding of the vascular endothelial cell heterogeneity and endothelial stem cells associated with angiogenesis and homeostasis in mice and humans, and we discuss future prospects for the application of scRNA-seq technology

Measurement and Analysis of Electromyography for Sequential Mastication

　In the palatability of food, texture is a major factor of food quality. The physical shear force value of meat has been measured. However, quantitative relationship and characterization between shear force value and tenderness as a sensory perception has not been clear. Therefore, a computer system was developed to analyze and to measure the electromyography (EMG) for mastication. 　The integral EMG values were almost constant by sequential mastication up to five times. The average of integral EMG values were 63.6 mV with tender meat of pork fillet and 153.8 mV with firm meat of beef round, giving a ratio of 2.4 times. The shear force values of similar samples were 2,300 g and 8,300 g each, and the ratio was 3.6 times. Sensory texture of the subjective feeling was 3ﾝ4 times that corresponded with the shear force value. The integral EMG value could be thought to compress the amount of texture sense. 　The integral EMG varied greatly in food, and showed lower value in order of boiled fish surimi, steamed fish paste, pork sausage, konnyaku (devil’s tongue), pork fillet, beef loin, pork ham portion, roast beef, pork loin and beef round. Generally this order reflected the sensory texture of chewing. The deviation of the integral EMG value was smaller than expected, so it has a definite possibility for practical use

Magnetic-field-induced spin crossover of Y-doped Pr0.7Ca0.3CoO3

The family of hole-doped Pr-based perovskite cobaltites, Pr0.5Ca0.5CoO3 and (Pr1−yREy)0.3Ca0.7CoO3 (where RE is rare earth), has recently been found to exhibit simultaneous metal-insulator, spin-state, and valence transitions. We have investigated magnetic-field-induced phase transitions of (Pr1−yYy)0.7Ca0.3CoO3 by means of magnetization measurements at 4.2–100 K up to an ultrahigh magnetic field of 140 T with the chemical pressure varied by y=0.0625, 0.075, 0.1. The observed magnetic-field-induced transitions were found to occur simultaneously with the metal-insulator transitions up to 100 T. The obtained magnetic-field-temperature (B−T) phase diagram and magnetization curves are well analyzed by a spin-crossover model of a single ion with interion interactions. On the other hand, the chemical pressure dependence of the experimentally obtained magnetization change during the phase transition disagrees with the single-ion model when approaching low temperatures. The significant y dependence of the magnetization change at low temperatures may arise from the itinerant magnetism of Co3+ in the paramagnetic metallic phase, where the chemical pressure enhances the exchange splitting by promoting the double-exchange interaction. The observed B−T phase diagrams of (Pr1−yYy)0.7Ca0.3CoO3 are quite contrary to that of LaCoO3, indicating that in (Pr1−yYy)0.7Ca0.3CoO3 the high-field phase possesses higher entropy than the low-field phase, whereas it is the other way around in LaCoO3

Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis

Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome remodeling and deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active lymphoid differentiation genes. Loss in Ikaros DNA binding activity caused a local increase in Mi-2β chromatin remodeling and histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributed to transcriptionally poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks

Task-Dependent Inhomogeneous Muscle Activities within the Bi-Articular Human Rectus Femoris Muscle

The motor nerve of the bi-articular rectus femoris muscle is generally split from the femoral nerve trunk into two sub-branches just before it reaches the distal and proximal regions of the muscle. In this study, we examined whether the regional difference in muscle activities exists within the human rectus femoris muscle during maximal voluntary isometric contractions of knee extension and hip flexion. Surface electromyographic signals were recorded from the distal, middle, and proximal regions. In addition, twitch responses were evoked by stimulating the femoral nerve with supramaximal intensity. The root mean square value of electromyographic amplitude during each voluntary task was normalized to the maximal compound muscle action potential amplitude (M-wave) for each region. The electromyographic amplitudes were significantly smaller during hip flexion than during knee extension task for all regions. There was no significant difference in the normalized electromyographic amplitude during knee extension among regions within the rectus femoris muscle, whereas those were significantly smaller in the distal than in the middle and proximal regions during hip flexion task. These results indicate that the bi-articular rectus femoris muscle is differentially controlled along the longitudinal direction and that in particular the distal region of the muscle cannot be fully activated during hip flexion