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Xiaojing Ma Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Hongfei Li Department of Biological Sciences, Mount Holyoke College, South Hadley, Massachusetts, USA

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Shuntian Zhu Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Zixuan Hong Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Weijing Kong Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Qihang Yuan Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Runlong Wu Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Zihang Pan Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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Jing Zhang Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, China

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Yahong Chen Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, China

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Xi Wang Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York, USA

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Kai Wang Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

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technologies from vascular biology, synthetic biology and bioengineering are being combined for nourishing the organoids with vasculature. The rapid progression of such interdisciplinary talk leads to the ‘angiorganoid’ in which the organoids are upgraded with

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Jordan C Langston Department of Bioengineering, Temple University, Philadelphia, Pennsylvania, USA

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Michael T Rossi Illumina, San Diego, California, USA

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Qingliang Yang Department of Mechanical Engineering, Temple University, Philadelphia, Pennsylvania, USA

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William Ohley Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA

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Edwin Perez Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA

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Laurie E Kilpatrick Center for Inflammation and Lung Research, Department of Microbiology, Immunology and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA

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Balabhaskar Prabhakarpandian Center for Inflammation and Lung Research, Department of Microbiology, Immunology and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA

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Mohammad F Kiani Department of Bioengineering, Temple University, Philadelphia, Pennsylvania, USA
Department of Mechanical Engineering, Temple University, Philadelphia, Pennsylvania, USA

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During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein–protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.

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Ana Correia-Branco Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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Ariel Mei Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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Sreehari Pillai Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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Nirmala Jayaraman Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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Radhika Sharma Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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Alison G Paquette University of Washington, Department of Pediatrics, Seattle, Washington, USA

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Naveen K Neradugomma Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA

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Ciara Benson Department of Bioengineering, University of Washington, Seattle, Washington, USA

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Nicholas W Chavkin Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA

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Qingcheng Mao Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA

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Mary C Wallingford Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, USA

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The placenta mediates the transport of nutrients, such as inorganic phosphate (Pi), between the maternal and fetal circulatory systems. The placenta itself also requires high levels of nutrient uptake as it develops to provide critical support for fetal development. This study aimed to determine placental Pi transport mechanisms using in vitro and in vivo models. We observed that Pi (P33) uptake in BeWo cells is sodium dependent and that SLC20A1/Slc20a1 is the most highly expressed placental sodium-dependent transporter in mouse (microarray), human cell line (RT-PCR) and term placenta (RNA-seq), supporting that normal growth and maintenance of the mouse and human placenta requires SLC20A1/Slc20a1. Slc20a1 wild-type (Slc20a1+/+ ) and knockout (Slc20a1–/– ) mice were produced through timed intercrosses and displayed yolk sac angiogenesis failure as expected at E10.5. E9.5 tissues were analyzed to test whether placental morphogenesis requires Slc20a1. At E9.5, the developing placenta was reduced in size in Slc20a1–/– . Multiple structural abnormalities were also observed in the Slc20a1–/– chorioallantois. We determined that monocarboxylate transporter 1 protein (MCT1+) cells were reduced in developing Slc20a1–/– placenta, confirming that Slc20a1 loss reduced trophoblast syncytiotrophoblast 1 (SynT-I) coverage. Next, we examined the cell type-specific Slc20a1 expression and SynT molecular pathways in silico and identified Notch/Wnt as a pathway of interest that regulates trophoblast differentiation. We further observed that specific trophoblast lineages express Notch/Wnt genes that associate with endothelial cell tip-and-stalk cell markers. In conclusion, our findings support that Slc20a1 mediates the symport of Pi into SynT cells, providing critical support for their differentiation and angiogenic mimicry function at the developing maternalfetal interface.

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Sheridan M Sargent Neuroscience Graduate Program, University of Washington, Seattle, Washington, USA

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Stephanie K Bonney Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA

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Yuandong Li Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA

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Stefan Stamenkovic Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA

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Marc M Takeno Allen Institute for Brain Science, Seattle, Washington, USA

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Vanessa Coelho-Santos Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Portugal
Institute of Nuclear Sciences Applied to Health, University of Coimbra, Portugal

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Andy Y Shih Neuroscience Graduate Program, University of Washington, Seattle, Washington, USA
Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA
Department of Pediatrics, University of Washington, Seattle, Washington, USA
Department of Bioengineering, University of Washington, Seattle, Washington, USA

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The high metabolic demand of brain tissue is supported by a constant supply of blood flow through dense microvascular networks. Capillaries are the smallest class of vessels in the brain and their lumens vary in diameter between ~2 and 5 μm. This diameter range plays a significant role in optimizing blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if the architecture of the endothelial wall also contributes to capillary diameter. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical mm3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of two to six interlocked endothelial cells, while the capillaries intervening these zones are composed of either one or two endothelial cells, with roughly equal proportions. The luminal area and diameter are on average slightly larger with capillary segments composed of two interlocked endothelial cells vs one endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, including pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.

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Jaana Schneider Ludwig-Boltzmann-Institute for Experimental and Clinical Traumatology, Vienna, Austria
Austrian Cluster for Tissue Regeneration, Vienna, Austria

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Marianne Pultar Ludwig-Boltzmann-Institute for Experimental and Clinical Traumatology, Vienna, Austria
Austrian Cluster for Tissue Regeneration, Vienna, Austria

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Wolfgang Holnthoner Ludwig-Boltzmann-Institute for Experimental and Clinical Traumatology, Vienna, Austria
Austrian Cluster for Tissue Regeneration, Vienna, Austria

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amniotic cells ( 24 ) making these cells attractive for tissue-specific vascular bioengineering. Table 1 Cell types used in co-culture models for microvascular network formation. Endothelial cell type Supporting cell type Reference

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Paolo Madeddu University of Bristol, Bristol, UK

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, oncology, vascular development, inflammation, wound healing and bioengineering. Manuscripts will be published online shortly after acceptance and the final version of record will be published as soon as it is ready, which means papers will be citable

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Ebba Brakenhielm Normandy University, UniRouen, Inserm (Institut National de la Santé et de la Recherche Médicale) UMR1096 (EnVI Laboratory), FHU REMOD-VHF, Rouen, France

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Vincent Richard Normandy University, UniRouen, Inserm (Institut National de la Santé et de la Recherche Médicale) UMR1096 (EnVI Laboratory), FHU REMOD-VHF, Rouen, France

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vessels in human patients. Although bioengineered vascular grafts are making considerable headway toward surgical macrovascular replacement or angioplasty ( 3 ), the finer vascular structures, including resistance arteries and arterioles, venules and

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Eleonora Zucchelli National Heart and Lung Institute, Imperial College London, London, UK

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Qasim A Majid National Heart and Lung Institute, Imperial College London, London, UK

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Gabor Foldes National Heart and Lung Institute, Imperial College London, London, UK
Heart and Vascular Center, Semmelweis University, Budapest, Hungary

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, variables, and selecting the right platform . Frontiers in Bioengineering and Biotechnology 2016 12 . ( https://doi.org/10.3389/fbioe.2016.00012 ) 64 Kim S Lee H Chung M Jeon NL . Engineering of functional, perfusable 3D microvascular

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Gloria Garoffolo Unità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino, IRCCS, Via Parea, Milan, Italy

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Maurizio Pesce Unità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino, IRCCS, Via Parea, Milan, Italy

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morphology . Biotechnology and Bioengineering 2012 109 695 – 707 . ( https://doi.org/10.1002/bit.24352 ) 19 Lieu DK Pappone PA Barakat AI . Differential membrane potential and ion current responses to different types of shear stress in

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Chia-Pei Denise Hsu Engineering Center, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA

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Joshua D Hutcheson Engineering Center, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA

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Sharan Ramaswamy Engineering Center, Department of Biomedical Engineering, Florida International University, Miami, Florida, USA

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Luxan G Driessen-Mol A Bouten C Baaijens F Pompa J . How to make a heart valve: from embryonic development to bioengineering of living valve substitutes. Cold Spring Harbor Perspectives in Medicine 2014 1 – 24 . 31 Heckel E Boselli

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