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      Stem Cells and Innate Immunity in Aquatic Invertebrates: Bridging Two Seemingly Disparate Disciplines for New Discoveries in Biology

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          Abstract

          The scopes related to the interplay between stem cells and the immune system are broad and range from the basic understanding of organism’s physiology and ecology to translational studies, further contributing to (eco)toxicology, biotechnology, and medicine as well as regulatory and ethical aspects. Stem cells originate immune cells through hematopoiesis, and the interplay between the two cell types is required in processes like regeneration. In addition, stem and immune cell anomalies directly affect the organism’s functions, its ability to cope with environmental changes and, indirectly, its role in ecosystem services. However, stem cells and immune cells continue to be considered parts of two branches of biological research with few interconnections between them. This review aims to bridge these two seemingly disparate disciplines towards much more integrative and transformative approaches with examples deriving mainly from aquatic invertebrates. We discuss the current understanding of cross-disciplinary collaborative and emerging issues, raising novel hypotheses and comments. We also discuss the problems and perspectives of the two disciplines and how to integrate their conceptual frameworks to address basic equations in biology in a new, innovative way.

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          Most cited references348

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          The single cell transcriptional landscape of mammalian organogenesis

          Mammalian organogenesis is an astonishing process. Within a short window of time, the cells of the three germ layers transform into an embryo that includes most major internal and external organs. Here we set out to investigate the transcriptional dynamics of mouse organogenesis at single cell resolution. With sci-RNA-seq3, we profiled ~2 million cells, derived from 61 embryos staged between 9.5 and 13.5 days of gestation, in a single experiment. The resulting ‘mouse organogenesis cell atlas’ (MOCA) provides a global view of developmental processes during this critical window. We identify hundreds of cell types and 56 trajectories, many of which are detected only because of the depth of cellular coverage, and collectively define thousands of corresponding marker genes. With Monocle 3, we explore the dynamics of gene expression within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle.
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            A role for mitochondria in NLRP3 inflammasome activation.

            An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
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              The microbiome and innate immunity.

              The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 June 2021
                2021
                : 12
                : 688106
                Affiliations
                [1] 1 Department of Biology, University of Padua , Padua, Italy
                [2] 2 Middle East Technical University, Institute of Marine Sciences, Erdemli , Mersin, Turkey
                [3] 3 Department of Clinical and Experimental Medicine, Unit of Experimental Biology and Genetics, University of Pisa , Pisa, Italy
                [4] 4 Department of Biology, Israel Oceanographic and Limnological Research, National Institute of Oceanography , Haifa, Israel
                [5] 5 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine , Stanford, CA, United States
                [6] 6 Department of Biology, Stanford University, Hopkins Marine Station , Pacific Grove, CA, United States
                [7] 7 Department of Biology, Chan Zuckerberg Biohub , San Francisco, CA, United States
                [8] 8 The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Center for Regenerative Medicine and Stem Cells, Ben-Gurion University of the Negev , Beer-Sheva, Israel
                [9] 9 Department of Earth Environment and Life Sciences (DISTAV), University of Genoa , Genoa, Italy
                [10] 10 Institute for Biomedical Research and Innovation, National Research Council , Palermo, Italy
                [11] 11 Department of Biology, Biotechnical Faculty, University of Ljubljana , Ljubljana, Slovenia
                [12] 12 Department of Environmental Science and Policy, University of Milan , Milan, Italy
                [13] 13 Department of Physical, Earth and Environmental Sciences, University of Siena , Siena, Italy
                Author notes

                Edited by: Geert Wiegertjes, Wageningen University and Research, Netherlands

                Reviewed by: Ricardo M. Zayas, San Diego State University, United States; Larry J. Dishaw, University of South Florida St. Petersburg, United States

                *Correspondence: Damjana Drobne, damjana.drobne@ 123456bf.uni-lj.si ; Loriano Ballarin, ballarin@ 123456bio.unipd.itbf.uni-lj.si

                This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.688106
                8278520
                af310359-43b7-4bba-8f2b-79eb05d8d8ec
                Copyright © 2021 Ballarin, Karahan, Salvetti, Rossi, Manni, Rinkevich, Rosner, Voskoboynik, Rosental, Canesi, Anselmi, Pinsino, Tohumcu, Jemec Kokalj, Dolar, Novak, Sugni, Corsi and Drobne

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 March 2021
                : 31 May 2021
                Page count
                Figures: 10, Tables: 0, Equations: 0, References: 348, Pages: 24, Words: 10286
                Funding
                Funded by: H2020 Industrial Leadership 10.13039/100010667
                Categories
                Immunology
                Review

                Immunology
                stem cells,immune cells,tissue regeneration,aquatic invertebrates,system biology,omics technology

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