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STAT3-Ser/Hes3 Signaling: a New Molecular Component of the Neuroendocrine System?
Review 77 STAT3-Ser/Hes3 Signaling: A New Molecular Component of the Neuroendocrine System? Authors P. Nikolakopoulou1, S. W. Poser1, J. Masjkur1, M. Fernandez Rubin de Celis1, L. Toutouna1, C. L. Andoniadou2, R. D. McKay3, G. Chrousos4, M. Ehrhart-Bornstein1, S. R. Bornstein1, A. Androutsellis-Theotokis1, 5, 6 Affiliations Affiliation addresses are listed at the end of the article Key words Abstract evidence suggests that a common non-canonical ●▶ STAT3 ▼ signaling pathway regulates adult progenitors in ●▶ Hes3 The endocrine system involves communication several different tissues, rendering it as a poten- ▶ stem cells ● among different tissues in distinct organs, includ- tially valuable starting point to explore their ing the pancreas and components of the Hypo- biology. The STAT3-Ser/Hes3 Signaling Axis was thalamic-Pituitary-Adrenal Axis. The molecular first identified as a major regulator of neural mechanisms underlying these complex interac- stem cells and, subsequently, cancer stem cells. In tions are a subject of intense study as they may the endocrine/neuroendocrine system, this path- hold clues for the progression and treatment of a way operates on several levels, regulating other variety of metabolic and degenerative diseases. A types of plastic cells: (a) it regulates pancreatic plethora of signaling pathways, activated by hor- islet cell function and insulin release; (b) insulin mones and other endocrine factors have been in turn activates the pathway in broadly distrib- implicated in this communication. Recent uted neural progenitors and possibly also hypo- advances in the stem cell field introduce a new thalamic tanycytes, cells with important roles in level of complexity: adult progenitor cells appear the control of the adrenal gland; (c) adrenal pro- to utilize distinct signaling pathways than the genitors themselves operate this pathway. -
The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models
biomolecules Review The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models Meera Krishnan 1, Sahil Kumar 1, Luis Johnson Kangale 2,3 , Eric Ghigo 3,4 and Prasad Abnave 1,* 1 Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Gurgaon-Faridabad Ex-pressway, Faridabad 121001, India; [email protected] (M.K.); [email protected] (S.K.) 2 IRD, AP-HM, SSA, VITROME, Aix-Marseille University, 13385 Marseille, France; [email protected] 3 Institut Hospitalo Universitaire Méditerranée Infection, 13385 Marseille, France; [email protected] 4 TechnoJouvence, 13385 Marseille, France * Correspondence: [email protected] Abstract: Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differ- entiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. -
Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation -
What, If Anything, Is Rodent Prefrontal Cortex?
Review Cognition and Behavior What, If Anything, Is Rodent Prefrontal Cortex? Mark Laubach,1 Linda M. Amarante,1 Kyra Swanson,1 and Samantha R. White1 https://doi.org/10.1523/ENEURO.0315-18.2018 1Department of Biology and Center for Behavioral Neuroscience, American University, Washington, DC 20016 Visual Abstract Prefrontal cortex (PFC) means different things to different people. In recent years, there has been a major increase in publications on the PFC, especially using mice. However, inconsistencies in the nomenclature and anatomical boundaries of PFC areas has made it difficult for researchers to compare data and interpret findings across species. We conducted a meta-analysis of publications on the PFC of humans and rodents and found dramatic differences in the focus of research on these species. In addition, we compared anatomical terms and criteria across several common rodent brain atlases and found inconsistencies among, and even within, leading atlases. To assess the impact of these issues on the research community, we conducted a survey of established PFC researchers on their use of anatomical terms and found little consensus. We report on the results of the survey and propose an alternative scheme for interpreting data Significance Statement Studies on prefrontal parts of the rodent cerebral cortex have appeared at an increasing rate in recent years. However, there has been no consensus on the terms used to describe the rodent prefrontal cortex (PFC) or how it relates to the PFC of monkeys and humans. To address these issues, we conducted a meta-analysis of publications on the PFC across species, a review of rodent brain atlases, a survey of PFC researchers on anatomic terms, and an analysis of how species differences in the corpus callosum might help relate PFC areas across species. -
The Virtual Mouse Brain: a Computational Neuroinformatics Platform to Study Whole Mouse Brain Dynamics
bioRxiv preprint doi: https://doi.org/10.1101/123406; this version posted April 3, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. The Virtual Mouse Brain: a computational neuroinformatics platform to study whole mouse brain dynamics Francesca Melozzi, Marmaduke M. Woodman, Viktor K. Jirsa∗, Christophe Bernard∗ Aix Marseille Univ, Inserm, INS, Institut de Neurosciences des Systèmes, Marseille, France ∗equally contributing last authors Correspondence author: [email protected] Abstract Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain’s structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain to whole mouse brain network modeling based on individual diffusion Magnetic Resonance Imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. The Virtual Mouse Brain enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions. Introduction -
Rh]DIAZEPAM BINDING in MAMMALIAN CENTRAL NERVOUS SYSTEM: a PHARMACOLOGICAL CHARACTERIZATION
0270-6474/81/0102-0218$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 1, No. 2, pp. 218-225 Printed in U.S.A. February 1981 rH]DIAZEPAM BINDING IN MAMMALIAN CENTRAL NERVOUS SYSTEM: A PHARMACOLOGICAL CHARACTERIZATION DOROTHY W. GALLAGER,*, ’ PIERRE MALLORGA,* WOLFGANG OERTEL,# RICHARD HENNEBERRY,$ AND JOHN TALLMAN* * Biological Psychiatry Branch, National Institute of Mental Health, $Laboratory of Clinical Science, National Institute of Mental Health, and SLaboratory of Molecular Biology, National Institute of General Medical Sciences, Bethesda, Maryland 20205 Abstract Two types of benzodiazepine binding sites for [3H]diazepam in mammalian central nervous tissue were identified using selective in vitro tissue culture and in situ kainic acid lesion techniques. These two binding sites were pharmacologically distinguished by differential displacement of the [3H]diazepam radioligand using the centrally active benzodiazepine, clonazepam, and the centrally inactive benzodiazepine, R05-4864. Clonazepam-displaceable binding sites were found to be located principally on neuronal membranes, while R05-4864-displaceable binding sites were found to be located on non-neuronal elements. These pharmacological distinctions can be used to characterize the predominant cell types which bind benzodiazepines in nervous tissue. It is suggested that one quantitative measure of different cell populations is the ratio of clonazepam- to R05-4864-displaceable [3H]diazepam binding within a single neuronal tissue sample. Binding sites for benzodiazepines in brain which have sites on the kidney cells, although possessing a high high affinity and show saturability and stereospecificity affinity for [3H]diazepam, showed an entirely different have been described (Squires and Braestrup, 1977; Moh- pharmacological spectrum from the brain site. -
The Distribution of Tyrosine Hydroxylase-Lmmunoreactive Fibers in Primate Neocortex Is Widespread but Regionally Specific
The Journal of Neuroscience, January 1987, 7(l): 279-290 The Distribution of Tyrosine Hydroxylase-lmmunoreactive Fibers in Primate Neocortex Is Widespread but Regionally Specific David A. Lewis,lea Michael J. Campbell,’ Stephen L. Foote, I.2 Menek Goldstein,3 and John H. Morrison’ ‘Scripps Clinic and Research Foundation, La Jolla, California 92037, 2Department of Psychiatry, University of California, San Diego, California 92037, and 3N.Y.U. Medical Center, New York, New York 10016 An antiserum directed against tyrosine hydroxylase (TH), an alleled by an elaboration and specialization of the noradrenergic enzyme involved in dopamine and norepinephrine synthe- and serotoninergic projections to neocortex. Compared to rat, sis, was used to visualize axons immunohistochemically in both of these systems in primates exhibit substantial regional monkey n’eocortex. Labeled fibers were distributed through- heterogeneity in the density and laminar distribution of cortical out the entire neocottex, but they had striking patterns of fibers (Brown et al., 1979; Morrison et al., 1982a, b; Takeuchi regional and laminar specialization. For example, primary and Sano, 1983). Midbrain dopaminergic neurons also project motor cortex contained the greatest density of TH-labeled to neocortex, but little is known about the distribution of do- fibers, whereas primary sensory regions were sparsely in- paminergic fibers in primate neocortex. Initial studies on the nervated. Marked heterogeneity of fiber density was also rat revealed that dopaminergic fibers were restricted to limited present among the association regions of the frontal, pari- portions of the prefrontal, cingulate, and perirhinal cortical re- etal, and temporal lobes. In addition, the laminar pattern of gions (Thierry et al., 1973; Berger et al., 1974, 1976; Fuxe et innervation in a given region was correlated with its fiber al., 1974; Hokfelt et al., 1974b; Lindvall et al., 1974). -
Pallial Origin of Basal Forebrain Cholinergic Neurons in the Nucleus
ERRATUM 4565 Development 138, 4565 (2011) doi:10.1242/dev.074088 © 2011. Published by The Company of Biologists Ltd Pallial origin of basal forebrain cholinergic neurons in the nucleus basalis of Meynert and horizontal limb of the diagonal band nucleus Ana Pombero, Carlos Bueno, Laura Saglietti, Monica Rodenas, Jordi Guimera, Alexandro Bulfone and Salvador Martinez There was an error in the ePress version of Development 138, 4315-4326 published on 24 August 2011. In Fig. 7P, the P-values are not given in the legend. For region 2, P=0.02; for region 3, P=0.003. The final online issue and print copy are correct. We apologise to authors and readers for this error. DEVELOPMENT RESEARCH ARTICLE 4315 Development 138, 4315-4326 (2011) doi:10.1242/dev.069534 © 2011. Published by The Company of Biologists Ltd Pallial origin of basal forebrain cholinergic neurons in the nucleus basalis of Meynert and horizontal limb of the diagonal band nucleus Ana Pombero1, Carlos Bueno1, Laura Saglietti2, Monica Rodenas1, Jordi Guimera3, Alexandro Bulfone4 and Salvador Martinez1,* SUMMARY The majority of the cortical cholinergic innervation implicated in attention and memory originates in the nucleus basalis of Meynert and in the horizontal limb of the diagonal band nucleus of the basal prosencephalon. Functional alterations in this system give rise to neuropsychiatric disorders as well as to the cognitive alterations described in Parkinson and Alzheimer’s diseases. Despite the functional importance of these basal forebrain cholinergic neurons very little is known about their origin and development. Previous studies suggest that they originate in the medial ganglionic eminence of the telencephalic subpallium; however, our results identified Tbr1-expressing, reelin-positive neurons migrating from the ventral pallium to the subpallium that differentiate into cholinergic neurons in the basal forebrain nuclei projecting to the cortex. -
Stem Cell Therapy and Gene Transfer for Regeneration
Gene Therapy (2000) 7, 451–457 2000 Macmillan Publishers Ltd All rights reserved 0969-7128/00 $15.00 www.nature.com/gt MILLENNIUM REVIEW Stem cell therapy and gene transfer for regeneration T Asahara, C Kalka and JM Isner Cardiovascular Research and Medicine, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA The committed stem and progenitor cells have been recently In this review, we discuss the promising gene therapy appli- isolated from various adult tissues, including hematopoietic cation of adult stem and progenitor cells in terms of mod- stem cell, neural stem cell, mesenchymal stem cell and ifying stem cell potency, altering organ property, accelerating endothelial progenitor cell. These adult stem cells have sev- regeneration and forming expressional organization. Gene eral advantages as compared with embryonic stem cells as Therapy (2000) 7, 451–457. their practical therapeutic application for tissue regeneration. Keywords: stem cell; gene therapy; regeneration; progenitor cell; differentiation Introduction poietic stem cells to blood cells. The determined stem cells differentiate into ‘committed progenitor cells’, which The availability of embryonic stem (ES) cell lines in mam- retain a limited capacity to replicate and phenotypic fate. malian species has greatly advanced the field of biologi- In the past decade, researchers have defined such com- cal research by enhancing our ability to manipulate the mitted stem or progenitor cells from various tissues, genome and by providing model systems to examine including bone marrow, peripheral blood, brain, liver cellular differentiation. ES cells, which are derived from and reproductive organs, in both adult animals and the inner mass of blastocysts or primordial germ cells, humans (Figure 1). -
Progenitor Cell Therapy for the Treatment of Damaged Myocardium
Progenitor Cell Therapy for the Treatment of Damaged Protocol Myocardium due to Ischemia (20218) Medical Benefit Effective Date: 01/01/11 Next Review Date: 07/22 Preauthorization No Review Dates: 09/10, 07/11, 07/12, 07/13, 07/14, 07/15, 07/16, 07/17, 07/18, 07/19, 07/20, 07/21 This protocol considers this test or procedure investigational. If the physician feels this service is medically necessary, preauthorization is recommended. The following protocol contains medical necessity criteria that apply for this service. The criteria are also applicable to services provided in the local Medicare Advantage operating area for those members, unless separate Medicare Advantage criteria are indicated. If the criteria are not met, reimbursement will be denied and the patient cannot be billed. Please note that payment for covered services is subject to eligibility and the limitations noted in the patient’s contract at the time the services are rendered. RELATED PROTOCOLS Orthopedic Applications of Stem Cell Therapy (Including Allograft and Bone Substitute Products Used With Autologous Bone Marrow) Stem Cell Therapy for Peripheral Arterial Disease Populations Interventions Comparators Outcomes Individuals: Interventions of interest Comparators of interest Relevant outcomes include: • With acute cardiac are: are: • Disease-specific survival ischemia • Progenitor cell therapy • Standard therapy • Morbid events • Functional outcomes • Quality of life • Hospitalizations Individuals: Interventions of interest Comparators of interest Relevant outcomes -
Differential Contributions of Haematopoietic Stem Cells to Foetal and Adult Haematopoiesis: Insights from Functional Analysis of Transcriptional Regulators
Oncogene (2007) 26, 6750–6765 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW Differential contributions of haematopoietic stem cells to foetal and adult haematopoiesis: insights from functional analysis of transcriptional regulators C Pina and T Enver MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK An increasing number of molecules have been identified ment and appropriate differentiation down the various as candidate regulators of stem cell fates through their lineages. involvement in leukaemia or via post-genomic gene dis- In the adult organism, HSC give rise to differentiated covery approaches.A full understanding of the function progeny following a series of relatively well-defined steps of these molecules requires (1) detailed knowledge of during the course of which cells lose proliferative the gene networks in which they participate and (2) an potential and multilineage differentiation capacity and appreciation of how these networks vary as cells progress progressively acquire characteristics of terminally differ- through the haematopoietic cell hierarchy.An additional entiated mature cells (reviewed in Kondo et al., 2003). layer of complexity is added by the occurrence of different As depicted in Figure 1, the more primitive cells in the haematopoietic cell hierarchies at different stages of haematopoietic differentiation hierarchy are long-term ontogeny.Beyond these issues of cell context dependence, repopulating HSC (LT-HSC), -
High-Resolution Data-Driven Model of the Mouse Connectome
RESEARCH High-resolution data-driven model of the mouse connectome Joseph E. Knox1,2, Kameron Decker Harris 2,3, Nile Graddis1, Jennifer D. Whitesell 1, Hongkui Zeng 1, Julie A. Harris1, Eric Shea-Brown 1,2, and Stefan Mihalas 1,2 1Allen Institute for Brain Science, Seattle, Washington, USA 2Applied Mathematics, University of Washington, Seattle, Washington, USA 3Computer Science and Engineering, University of Washington, Seattle, Washington, USA Keywords: Connectome, Whole-brain, Mouse an open access journal ABSTRACT Knowledge of mesoscopic brain connectivity is important for understanding inter- and intraregion information processing. Models of structural connectivity are typically constructed and analyzed with the assumption that regions are homogeneous. We instead use the Allen Mouse Brain Connectivity Atlas to construct a model of whole-brain connectivity at the scale of 100 µm voxels. The data consist of 428 anterograde tracing experiments in wild type C57BL/6J mice, mapping fluorescently labeled neuronal projections brain-wide. Inferring spatial connectivity with this dataset is underdetermined, since the approximately 2 × 105 source voxels outnumber the number of experiments. Citation: Knox, J. E., Harris, K. D., To address this issue, we assume that connection patterns and strengths vary smoothly Graddis, N., Whitesell, J. D., Zeng, H., Harris, J. A., Shea-Brown, E., & across major brain divisions. We model the connectivity at each voxel as a radial basis Mihalas, S. (2019). High-resolution data-driven model of the mouse kernel-weighted average of the projection patterns of nearby injections. The voxel model connectome. Network Neuroscience, outperforms a previous regional model in predicting held-out experiments and compared 3(1), 217–236.