Transcriptomic Changes Throughout Post-Hatch Development in Gallus Gallus Pituitary
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Strategies to Increase ß-Cell Mass Expansion
This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Strategies to increase -cell mass expansion Drynda, Robert Lech Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 Strategies to increase β-cell mass expansion A thesis submitted by Robert Drynda For the degree of Doctor of Philosophy from King’s College London Diabetes Research Group Division of Diabetes & Nutritional Sciences Faculty of Life Sciences & Medicine King’s College London 2017 Table of contents Table of contents ................................................................................................. -
The Transcription Factor Pou3f1 Promotes Neural Fate Commitment
RESEARCH ARTICLE elifesciences.org The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways Qingqing Zhu1,2†, Lu Song1†, Guangdun Peng1, Na Sun3, Jun Chen1, Ting Zhang1, Nengyin Sheng1, Wei Tang1, Cheng Qian1, Yunbo Qiao1, Ke Tang4, Jing-Dong Jackie Han3, Jinsong Li1, Naihe Jing1* 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 2Department of Neurosurgery, West China Hospital, Sichuan University, Sichuan, China; 3Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 4Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China Abstract The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors. However, how these two events are integrated to ensure appropriate neural conversion remains unclear. In this study, we showed that Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown leads to a markedly decreased *For correspondence: njing@ incorporation of ESCs in the neuroectoderm. By contrast, Pou3f1-overexpressing ESC derivatives sibcb.ac.cn preferentially contribute to the neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses †These authors contributed indicated that Pou3f1 is an upstream activator of neural lineage genes, and also is a repressor of equally to this work BMP and Wnt signaling. -
Redirecting Intracellular Trafficking and the Secretion Pattern of FSH Dramatically Enhances Ovarian Function in Mice
Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice Huizhen Wanga, Melissa Larsona, Albina Jablonka-Shariffb, Christopher A. Pearlb, William L. Millerc, P. Michael Connd, Irving Boimeb, and T. Rajendra Kumara,e,1 Departments of aMolecular and Integrative Physiology and ePathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160; bDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110; cDepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695; and dDepartments of Internal Medicine and Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430 Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved February 28, 2014 (received for review November 14, 2013) FSH and luteinizing hormone (LH) are secreted constitutively or in Results pulses, respectively, from pituitary gonadotropes in many vertebrates, Strategy to Redirect FSH from the Constitutive to Regulated Pathway. Our and regulate ovarian function. The molecular basis for this evolution- in vitro screens indicated that a carboxyterminal (C′)-heptapeptide arily conserved gonadotropin-specific secretion pattern is not un- in the human LHβ (LSGLLFL) (12) or a modified FSHβ con- derstood. Here, we show that the carboxyterminal heptapeptide in taining this peptide (13) favors secretion of corresponding dimers LH is a gonadotropin-sorting determinant in vivo that directs pulsatile via the regulated pathway in heterologous somatotrope cells. secretion. FSH containing this heptapeptide enters the regulated Based on these initial data, we engineered human transgenes en- pathway in gonadotropes of transgenic mice, and is released in β ′ response to gonadotropin-releasing hormone, similar to LH. -
Disruption of the Neuronal PAS3 Gene in a Family Affected with Schizophrenia D Kamnasaran, W J Muir, M a Ferguson-Smith,Dwcox
325 ORIGINAL ARTICLE J Med Genet: first published as 10.1136/jmg.40.5.325 on 1 May 2003. Downloaded from Disruption of the neuronal PAS3 gene in a family affected with schizophrenia D Kamnasaran, W J Muir, M A Ferguson-Smith,DWCox ............................................................................................................................. J Med Genet 2003;40:325–332 Schizophrenia and its subtypes are part of a complex brain disorder with multiple postulated aetiolo- gies. There is evidence that this common disease is genetically heterogeneous, with many loci involved. See end of article for In this report, we describe a mother and daughter affected with schizophrenia, who are carriers of a authors’ affiliations t(9;14)(q34;q13) chromosome. By mapping on flow sorted aberrant chromosomes isolated from lym- ....................... phoblast cell lines, both subjects were found to have a translocation breakpoint junction between the Correspondence to: markers D14S730 and D14S70, a 683 kb interval on chromosome 14q13. This interval was found to Dr D W Cox, 8-39 Medical contain the neuronal PAS3 gene (NPAS3), by annotating the genomic sequence for ESTs and perform- Sciences Building, ing RACE and cDNA library screenings. The NPAS3 gene was characterised with respect to the University of Alberta, genomic structure, human expression profile, and protein cellular localisation to gain insight into gene Edmonton, Alberta T6G function. The translocation breakpoint junction lies within the third intron of NPAS3, resulting in the dis- 2H7, Canada; [email protected] ruption of the coding potential. The fact that the bHLH and PAS domains are disrupted from the remain- ing parts of the encoded protein suggests that the DNA binding and dimerisation functions of this Revised version received protein are destroyed. -
Selective Estrogen Receptor Modulators: Discrimination of Agonistic Versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells
[CANCER RESEARCH 64, 1522–1533, February 15, 2004] Selective Estrogen Receptor Modulators: Discrimination of Agonistic versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells Jonna Frasor,1 Fabio Stossi,1 Jeanne M. Danes,1 Barry Komm,2 C. Richard Lyttle,2 and Benita S. Katzenellenbogen1 1Department of Molecular and Integrative Physiology, University of Illinois and College of Medicine, Urbana, Illinois, and 2Women’s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania ABSTRACT tures in these women; however, some detrimental side effects such as an increased risk of endometrial cancer, stroke, and pulmonary embolism Selective estrogen receptor modulators (SERMs) such as tamoxifen are were also associated with tamoxifen treatment (7). Ral was examined in effective in the treatment of many estrogen receptor-positive breast cancers the Multiple Outcomes of Raloxifene Evaluation trial and found to be and have also proven to be effective in the prevention of breast cancer in women at high risk for the disease. The comparative abilities of tamoxifen effective in reducing the incidence of osteoporosis in postmenopausal versus raloxifene in breast cancer prevention are currently being compared in women, as well as the incidence of breast cancer but, unlike tamoxifen, the Study of Tamoxifen and Raloxifene trial. To better understand the actions without the increased risk of endometrial cancer (8, 9). On the basis of the of these compounds in breast cancer, we have examined their effects on the positive outcome of these trials, the Study of Tamoxifen and Raloxifene expression of ϳ12,000 genes, using Affymetrix GeneChip microarrays, with trial was begun in 1999 to directly compare the effects of these two quantitative PCR verification in many cases, categorizing their actions as SERMs, tamoxifen and Ral, in prevention of breast cancer (10, 11). -
Hes5 Regulates the Transition Timing of Neurogenesis and Gliogenesis In
© 2017. Published by The Company of Biologists Ltd | Development (2017) 144, 3156-3167 doi:10.1242/dev.147256 RESEARCH ARTICLE Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development Shama Bansod1,2, Ryoichiro Kageyama1,2,3,4 and Toshiyuki Ohtsuka1,2,3,* ABSTRACT has been reported that the high mobility group AT-hook (Hgma) During mammalian neocortical development, neural stem/progenitor genes regulate gene expression by modulating chromatin structure cells (NSCs) sequentially give rise to deep layer neurons and (Ozturk et al., 2014), maintain neurogenic NSCs, and inhibit superficial layer neurons through mid- to late-embryonic stages, gliogenesis during early- to mid-embryonic stages through global shifting to gliogenic phase at perinatal stages. Previously, we found opening of the chromatin state (Kishi et al., 2012). However, the that the Hes genes inhibit neuronal differentiation and maintain mechanism by which the expression of these epigenetic factors is NSCs. Here, we generated transgenic mice that overexpress Hes5 in controlled remains to be analyzed. NSCs of the central nervous system, and found that the transition Here, we found that Hes5, a transcriptional repressor acting timing from deep to superficial layer neurogenesis was shifted earlier, as an effector of Notch signaling, regulates the timing of while gliogenesis precociously occurred in the developing neocortex neurogenesis and gliogenesis via alteration in the expression of Hes5-overexpressing mice. By contrast, the transition from deep to levels of epigenetic factors. Notch signaling contributes to the superficial layer neurogenesis and the onset of gliogenesis were elaboration of cellular diversity during the development of various delayed in Hes5 knockout (KO) mice. -
Dynamic Gnrh and Hcg Testing: Establishment of New Diagnostic Reference Levels
176:4 PROOF ONLY A K Bang and others Reference levels on GnRH and 176:4 379–391 Clinical Study hCG tests Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels A Kirstine Bang1,2, Loa Nordkap1,2, Kristian Almstrup1,2, Lærke Priskorn1,2, Jørgen Holm Petersen1,2,3, Ewa Rajpert-De Meyts1,2, Anna-Maria Andersson1,2, Anders Juul1,2 and Niels Jørgensen1,2 1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Correspondence Denmark, 2International Center for Research and Research Training in Endocrine Disruption of Male should be addressed Reproduction and Child Health (EDMaRC), Rigshospitalet, Denmark, and 3Department of Biostatistics, to N Jørgensen University of Copenhagen, Copenhagen, Denmark Email [email protected] Abstract Objective: Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after GnRH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses. Design: GnRH and hCG stimulation tests were performed on 77 healthy men, 18–40 years (reference group) at a specialized andrology referral center at a university hospital. The potential influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic–pituitary–gonadal axis. Methods: Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC–MS/MS. Results: For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. -
Transcription Factor P73 Regulates Th1 Differentiation
ARTICLE https://doi.org/10.1038/s41467-020-15172-5 OPEN Transcription factor p73 regulates Th1 differentiation Min Ren1, Majid Kazemian 1,4, Ming Zheng2, JianPing He3, Peng Li1, Jangsuk Oh1, Wei Liao1, Jessica Li1, ✉ Jonathan Rajaseelan1, Brian L. Kelsall 3, Gary Peltz 2 & Warren J. Leonard1 Inter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing to these response differ- 1234567890():,; ences, here we analyze in vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects Th1 differentiation. In cells differentiated under Th1 conditions in vitro, p73 negatively regulates IFNγ production. p73 binds within, or upstream of, and modulates the expression of Th1 differentiation-related genes such as Ifng and Il12rb2. Furthermore, in mouse experimental autoimmune encephalitis, p73-deficient mice have increased IFNγ production and less dis- ease severity, whereas in an adoptive transfer model of inflammatory bowel disease, transfer of p73-deficient naïve CD4+ T cells increases Th1 responses and augments disease severity. Our results thus identify p73 as a negative regulator of the Th1 immune response, suggesting that p73 dysregulation may contribute to susceptibility to autoimmune disease. 1 Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-1674, USA. 2 Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. 4Present address: Department of Biochemistry and Computer Science, Purdue University, West ✉ Lafayette, IN 37906, USA. -
The Title of the Dissertation
UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic -
Single-Cell Sequencing of Human Ipsc-Derived Cerebellar Organoids Shows Recapitulation of Cerebellar Development
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.01.182196; this version posted July 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Single-cell sequencing of human iPSC-derived cerebellar organoids shows recapitulation of cerebellar development Samuel Nayler1*, Devika Agarwal3, Fabiola Curion2, Rory Bowden2,4, Esther B.E. Becker1,5* 1Department of Physiology, Anatomy and Genetics; University of Oxford; Oxford, OX1 3PT; United Kingdom 2Wellcome Centre for Human Genetics; University of Oxford; Oxford, OX3 7BN; United Kingdom 3Weatherall Institute for Molecular Medicine; University of Oxford; Oxford, OX3 7BN; United Kingdom 4Present address: Walter and Eliza Hall Institute of Medical Research, Parkville Victoria 3052; Australia 5Lead contact *Correspondence: [email protected], [email protected] Running title: hiPSC-derived cerebellar organoids 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.01.182196; this version posted July 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Current protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) are reliant on animal co-culture and mostly exist as monolayers, which have limited capability to recapitulate the complex arrangement of the brain. We developed a method to differentiate hPSCs into cerebellar organoids that display hallmarks of in vivo cerebellar development. Single- cell profiling followed by comparison to an atlas of the developing murine cerebellum revealed transcriptionally-discrete populations encompassing all major cerebellar cell types. -
Abstracts from the 9Th Biennial Scientific Meeting of The
International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):15 DOI 10.1186/s13633-017-0054-x MEETING ABSTRACTS Open Access Abstracts from the 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society (APPES) and the 50th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE) Tokyo, Japan. 17-20 November 2016 Published: 28 Dec 2017 PS1 Heritable forms of primary bone fragility in children typically lead to Fat fate and disease - from science to global policy a clinical diagnosis of either osteogenesis imperfecta (OI) or juvenile Peter Gluckman osteoporosis (JO). OI is usually caused by dominant mutations affect- Office of Chief Science Advsor to the Prime Minister ing one of the two genes that code for two collagen type I, but a re- International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):PS1 cessive form of OI is present in 5-10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that Attempts to deal with the obesity epidemic based solely on adult be- play a role in the processing of collagen type I protein (BMP1, havioural change have been rather disappointing. Indeed the evidence CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, PLOD2, SERPINF1, that biological, developmental and contextual factors are operating SERPINH1, SEC24D, SPARC, from the earliest stages in development and indeed across generations TMEM38B), or interfere with osteoblast function (SP7, WNT1). Specific is compelling. The marked individual differences in the sensitivity to the phenotypes are caused by mutations in SERPINF1 (recessive OI type obesogenic environment need to be understood at both the individual VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter and population level. -
SOX3 Is Required During the Formation of the Hypothalamo-Pituitary Axis
ARTICLES SOX3 is required during the formation of the hypothalamo-pituitary axis Karine Rizzoti1,5, Silvia Brunelli1,4,5, Danielle Carmignac2, Paul Q Thomas3, Iain C Robinson2 & Robin Lovell-Badge1 The pituitary develops from the interaction of the infundibulum, a region of the ventral diencephalon, and Rathke’s pouch, a derivative of oral ectoderm. Postnatally, its secretory functions are controlled by hypothalamic neurons, which also derive from the ventral diencephalon. In humans, mutations affecting the X-linked transcription factor SOX3 are associated with hypopituitarism and mental retardation, but nothing is known of their etiology. We find that deletion of Sox3 in mice leads to defects of pituitary function and of specific central nervous system (CNS) midline structures. Cells in the ventral diencephalon, where Sox3 is usually http://www.nature.com/naturegenetics highly expressed, have altered properties in mutant embryos, leading to abnormal development of Rathke’s pouch, which does not express the gene. Pituitary and hypothalamic defects persist postnatally, and SOX3 may also function in a subset of hypothalamic neurons. This study shows how sensitive the pituitary is to subtle developmental defects and how one gene can act at several levels in the hypothalamic-pituitary axis. The development of complex organs composed of different cell types review see ref. 5), is implicated in a syndrome of X-linked hypopitu- frequently depends on reciprocal induction events occurring between itarism and mental retardation6. In a single family whose males were distinct tissue layers that lie adjacent to one another in the embryo. deficient in growth hormone, a mutation in SOX3 was identified.