Basic Concepts of Development Potency
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Determination of Cell Development, Differentiation and Growth
Pediat. Res. I: 395-408 (1967) Determination of Cell Development, Differentiation and Growth A Review D.M.BROWN[ISO] Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA Introduction plasmic synthesis, water uptake, or, in the case of intact tissue, intercellular deposition. It may include prolifera It has become increasingly apparent that the basis for tion or the multiplication of identical cells and may be biologic variation in relation to disease states is in accompanied by differentiation which implies anatomical large part predetermined from early embryonic stages. as well as functional changes. The number of cellular Consideration of variations of growth and development units in a tissue may be related to the deoxyribonucleic must take into account the genetic constitution and acid (DNA) content or nucleocytoplasmic units [24, early embryonic events of tissue and organ develop 59, 143]. Differentiation may refer to physical and ment. chemical organization of subcellular components or The incidence of congenital malformation has been to changes in the structure and organization of cells estimated to be 2 to 3 percent of all live born infants and leading to specialized organs. may double by one year [133]. Minor abnormalities are even more common [79]. Furthermore, the large variety of well-defined 'inborn errors of metabolism', Control of Embryonic Chemical Development as well as the less apparent molecular and chromosomal abnormalities, should no doubt be considered as mal Protein syntheses during oogenesis and embryogenesis formations despite the possible lack of gross somatic are guided by nuclear and nucleolar ribonucleic acid aberrations. Low birth weight is a frequent accom (RNA) which are in turn controlled by primer DNA. -
Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery
University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 5-2021 Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery David Alfonso Castilla-Casadiego University of Arkansas, Fayetteville Follow this and additional works at: https://scholarworks.uark.edu/etd Part of the Polymer and Organic Materials Commons, and the Polymer Science Commons Citation Castilla-Casadiego, D. A. (2021). Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery. Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/3964 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected]. Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Engineering with a concentration in Chemical Engineering by David Alfonso Castilla-Casadiego Atlantic University Bachelor of Science in Chemical Engineering, 2011 University of Puerto Rico – Mayagüez Campus Master of Science in Chemical Engineering, 2016 May 2021 University of Arkansas This dissertation is approved for recommendation to the Graduate Council. ____________________________________ Jorge L. Almodóvar-Montañez, Ph.D. Dissertation Director ____________________________________ _________________________________ -
Theory and Practice of Lineage Tracing
REGENERATIVE MEDICINE Theory and Practice of Lineage Tracing a,b YA-CHIEH HSU Key Words. Cell surface markers • Stem cell-microenvironment interactions • Cell cycle • Cell biology • Adult stem cells aDepartment of Stem Cell ABSTRACT and Regenerative Biology, Lineage tracing is a method that delineates all progeny produced by a single cell or a group of Harvard University, cells. The possibility of performing lineage tracing initiated the field of Developmental Biology Cambridge, Massachusetts, and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a suc- USA; bHarvard Stem Cell cessful lineage-tracing experiment. In addition, I summarize and compare different methods for Institute, Cambridge, conducting lineage tracing and provide examples of how these strategies can be implemented Massachusetts, USA to answer fundamental questions in development and regeneration. The advantages and limita- Correspondence: Ya-Chieh Hsu, tions of each method are also discussed. STEM CELLS 2015;33:3197–3204 Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Ave., SIGNIFICANCE STATEMENT Cambridge, Massachusetts 02138, USA. Telephone: Lineage relationships allow one to understand the cellular hierarchy of a tissue or organ, which (617) 496-3757; Fax: (617) 496- is central to both Developmental Biology and Stem Cell Biology. Different approaches have 3763; e-mail: yachiehhsu@fas. been developed to conduct lineage tracing. Understanding the underlying basis of these harvard.edu approaches, as well as their advantages and limitations, will allow one to choose the most Received March 26, 2015; appropriate method for a given question. accepted for publication June 23, 2015; first published online STEM CELLS in EXPRESS August 3, cells that are marked at the initial time point, 2015. -
Boosting the Cellular Potency of Embryonic Stem Cells by Spliceosome Targeting ✉ Wilfried A
Signal Transduction and Targeted Therapy www.nature.com/sigtrans RESEARCH HIGHLIGHT OPEN Boosting the cellular potency of embryonic stem cells by spliceosome targeting ✉ Wilfried A. Kues1 Signal Transduction and Targeted Therapy (2021) 6:324; https://doi.org/10.1038/s41392-021-00743-9 In recent work published in Cell, Shen et al.1 identified transfected ES cells with short interfering RNAs against different spliceosome inhibition in embryonic stem (ES) cells as a key spliceosome transcripts (the spliceosome consisted of 5 core and mechanism for the transition from pluri- to totipotency. Spliceo- several cofactor subunits, here 14 transcripts were targeted), some inhibition, achieved by RNA interference or the chemical respectively. Transient repression of 10 of the 14 splicing factors inhibitor pladienolide B, may gain widespread relevance to the resulted in ES cells, which maintained the typical colony culture of totipotent ES cells, in vitro differentiation of extra- morphology, however, pluripotent marker genes—Oct4 (Pou5f1), embryonal tissue and organoids, translation to the maintenance of Nanog, Sox2, Zfp42 and others—became down-regulated, at the pluripotent cells of other mammal species, including humans, and same time marker genes of totipotency—particularly Zscan4s and a better molecular understanding of cellular potency in stem cells MERVL—were up-regulated. Zscan4s (Zink finger and SCAN and cancer. domain containing 4) is a transcription factor and MERVL (murine The first successful isolation and maintenance of ES derived endogenous retrovirus L) an endogenous retrovirus with a usually fi 1234567890();,: from the inner cell mass (ICM) of murine blastocyst stages was restricted expression to 2-cell embryos. These results were veri ed described in 1981,2 and since then acted as game changer for by supplementing the culture medium with pladienolide B, a genetic studies in this mammalian model organism. -
Delta-Notch Signaling: the Long and the Short of a Neuron’S Influence on Progenitor Fates
Journal of Developmental Biology Review Delta-Notch Signaling: The Long and the Short of a Neuron’s Influence on Progenitor Fates Rachel Moore 1,* and Paula Alexandre 2,* 1 Centre for Developmental Neurobiology, King’s College London, London SE1 1UL, UK 2 Developmental Biology and Cancer, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK * Correspondence: [email protected] (R.M.); [email protected] (P.A.) Received: 18 February 2020; Accepted: 24 March 2020; Published: 26 March 2020 Abstract: Maintenance of the neural progenitor pool during embryonic development is essential to promote growth of the central nervous system (CNS). The CNS is initially formed by tightly compacted proliferative neuroepithelial cells that later acquire radial glial characteristics and continue to divide at the ventricular (apical) and pial (basal) surface of the neuroepithelium to generate neurons. While neural progenitors such as neuroepithelial cells and apical radial glia form strong connections with their neighbours at the apical and basal surfaces of the neuroepithelium, neurons usually form the mantle layer at the basal surface. This review will discuss the existing evidence that supports a role for neurons, from early stages of differentiation, in promoting progenitor cell fates in the vertebrates CNS, maintaining tissue homeostasis and regulating spatiotemporal patterning of neuronal differentiation through Delta-Notch signalling. Keywords: neuron; neurogenesis; neuronal apical detachment; asymmetric division; notch; delta; long and short range lateral inhibition 1. Introduction During the development of the central nervous system (CNS), neurons derive from neural progenitors and the Delta-Notch signaling pathway plays a major role in these cell fate decisions [1–4]. -
Molecular Cell and Developmental Biology Graduate Program 2018-2019
Molecular Cell and Developmental Biology Graduate Program 2018-2019 The Ph.D. track in Molecular Cell and Developmental Biology (MCD) is designed to prepare students for productive careers in biological research and teaching. This training program emphasizes applying diverse approaches, including biochemistry, genetics, genomics, and imaging, to addressing critical questions in molecular, cellular, and developmental biology. Interdisciplinary research is encouraged and supported by a diverse group of faculty from the Departments of Molecular Cell & Developmental Biology (MCD), Chemistry & Biochemistry (Chem), Microbiology & Environmental Toxicology (METX), Biomolecular Engineering (BME), the Santa Cruz Institute for Particle Physics (Physics), and Ecology & Evolutionary Biology (EEB). MCD Faculty James Ackman Visualizing structured activity throughout the developing vertebrate brain Manny Ares Mechanisms and regulation of splicing machinery; structure and function of small RNAs Joshua Arribere Analyzing RNA quality control in C. elegans Needhi Bhalla Meiotic chromosome dynamics Hinrich Boeger Chromatin structure and gene regulation Barry Bowman Membrane biochemistry, genetics, and molecular biology Susan Carpenter Long non-coding RNAs in innate immunity Bin Chen Molecular control of neuronal identity and connectivity in mammalian brains David Feldheim Topographic mapping in vertebrates/CNS Grant Hartzog Chromatin and transcription Lindsay Hinck Molecular basis of neuronal chemotropism Melissa Jurica Structural approaches to large macromolecular -
Engineering Lineage Potency and Plasticity of Stem Cells Using Epigenetic Molecules Received: 13 December 2017 Anandika Dhaliwal1, Sandra Pelka1, David S
www.nature.com/scientificreports OPEN Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules Received: 13 December 2017 Anandika Dhaliwal1, Sandra Pelka1, David S. Gray1 & Prabhas V. Moghe 1,2 Accepted: 11 October 2018 Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional Published: xx xx xxxx tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue- specifc lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating molecules can modulate the stem cell’s developmental program, and thus potentially overcome the limited lineage diferentiation that human stem cells exhibit based on the source and processing of stem cells. In this study, we screened a library of 84 small molecule pharmacological agents indicated in nucleosomal modifcation and identifed a sub-set of specifc molecules that infuenced osteogenesis in human mesenchymal stem cells (hMSCs) while maintaining cell viability in-vitro. Pre-treatment with fve candidate hits, Gemcitabine, Decitabine, I-CBP112, Chidamide, and SIRT1/2 inhibitor IV, maximally enhanced osteogenesis in-vitro. In contrast, fve distinct molecules, 4-Iodo-SAHA, Scriptaid, AGK2, CI-amidine and Delphidine Chloride maximally inhibited osteogenesis. We then tested the role of these molecules on hMSCs derived from aged human donors and report that small epigenetic molecules, namely Gemcitabine and Chidamide, can signifcantly promote osteogenic diferentiation by 5.9- and 2.3-fold, respectively. Taken together, this study demonstrates new applications of identifed small molecule drugs for sensitively regulating the lineage plasticity fates of bone-marrow derived mesenchymal stem cells through modulating the epigenetic profle of the cells. -
The Homeobox Gene GLABRA 2 Is Required for Position-Dependent Cell Differentiation in the Root Epidermis of Arabidopsis Thaliana
Development 122, 1253-1260 (1996) 1253 Printed in Great Britain © The Company of Biologists Limited 1996 DEV0049 The homeobox gene GLABRA 2 is required for position-dependent cell differentiation in the root epidermis of Arabidopsis thaliana James D. Masucci1, William G. Rerie2, Daphne R. Foreman1,†, Meng Zhang1, Moira E. Galway1,‡, M. David Marks3 and John W. Schiefelbein1,* 1Department of Biology, University of Michigan, Ann Arbor, MI 48109, USA 2Plant Research Centre, Agriculture Canada, Ottawa, Ontario K1A 0C6, Canada 3Department of Genetics and Cell Biology, University of Minnesota, St. Paul, MN 55108, USA *Author for correspondence (e-mail: [email protected]) †Present address: Department of Biology, Macalester University, St. Paul, MN 55105, USA ‡Present address: Department of Biology, St. Francis Xavier University, Antigonish, Nova Scotia B2G 2W5, Canada SUMMARY The role of the Arabidopsis homeobox gene, GLABRA 2 hairs, they are similar to atrichoblasts of the wild type in (GL2), in the development of the root epidermis has been their cytoplasmic characteristics, timing of vacuolation, investigated. The wild-type epidermis is composed of two and extent of cell elongation. The results of in situ nucleic cell types, root-hair cells and hairless cells, which are acid hybridization and GUS reporter gene fusion studies located at distinct positions within the root, implying that show that the GL2 gene is preferentially expressed in the positional cues control cell-type differentiation. During the differentiating hairless cells of the wild type, during a development of the root epidermis, the differentiating root- period in which epidermal cell identity is believed to be hair cells (trichoblasts) and the differentiating hairless cells established. -
Regulation of Growth and Cellular Differentiation In
Amer. J. Bot. 56(8): 918-927. 1969. REGULATION OF GROWTH AND CELLULAR DIFFERENTIATIOK IN DEVELOPING AVENA INTERNODES BY GIBBERELLIC ACID AND INDOLE-3-ACETIC ACID! PETER B. KAUFMAN, LOUISE B. PETERING, AND PAUL A. ADAMS Department of Botany, University of Michigan, Ann Arbor ABSTRACT Auxin (IAA) at physiological concentrations causes significant reduction of GA.-promoted growth in excised Avtna stem segments. IAA is thus considered to be a gibberellin antagonist in this system. It was found to act non-competitively in repressing GA.-augmented growth in these segments. In intercalary meristem cells at the base of the elongating internode, GA. blocks cell division activity and causes a marked increase in cell lengthening. IAA substantially pro motes lateral expansion in comparable intercalary meristem cells, particularly in the vicinity '" of vascular bundles underlying the epidermis. It also alters the plane of cell division in differentia ting stomata. IAA at high concentrations (10-', 10-4M), in combination with GA., overrides the effects of GA. on cell lengthening, while with low concentrations of IAA (10-', 10-10 M), the effects of GA:! are clearly dominant. At intermediate concentrations of IAA (10- 6, 10- 7 M), in the presence of G.<\" the effects of this treatment on cell differentiation closely parallel the pattern of differentiation in untreated tissue. It is postulated that a lateral gradient of auxin and gib berellin could control cell expansion in long epidermal cells during intercalary growth of the internode. RECENTLY, we reported that exogenously supplied MATERIALS AND METHoDs-Next-to-last inter gibberellic acid (GA 3) markedly accelerates the nodes (here designated as p-1; illustrated in Fig. -
Metabolic Regulation of Epigenetic Modifications and Cell
cancers Review Metabolic Regulation of Epigenetic Modifications and Cell Differentiation in Cancer Pasquale Saggese 1, Assunta Sellitto 2 , Cesar A. Martinez 1, Giorgio Giurato 2 , Giovanni Nassa 2 , Francesca Rizzo 2 , Roberta Tarallo 2 and Claudio Scafoglio 1,* 1 Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; [email protected] (P.S.); [email protected] (C.A.M.) 2 Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi (SA), Italy; [email protected] (A.S.); [email protected] (G.G.); [email protected] (G.N.); [email protected] (F.R.); [email protected] (R.T.) * Correspondence: [email protected]; Tel.: +1-310-825-9577 Received: 20 October 2020; Accepted: 11 December 2020; Published: 16 December 2020 Simple Summary: Cancer cells change their metabolism to support a chaotic and uncontrolled growth. In addition to meeting the metabolic needs of the cell, these changes in metabolism also affect the patterns of gene activation, changing the identity of cancer cells. As a consequence, cancer cells become more aggressive and more resistant to treatments. In this article, we present a review of the literature on the interactions between metabolism and cell identity, and we explore the mechanisms by which metabolic changes affect gene regulation. This is important because recent therapies under active investigation target both metabolism and gene regulation. The interactions of these new therapies with existing chemotherapies are not known and need to be investigated. -
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). -
Cell Fate and Cell Morphogenesis in Higher Plants
Cell fate and cell morphogenesis in higher plants John W Schiefelbein University of Michigan, Ann Arbor, USA The differentiation of plant cells depends on the regulation of cell fate and cell morphogenesis. Recent studies have led to the identification of mutants and the cloning of genes that influence these processes. In several instances, the genes encode products with homeodomains or Myb or Myc DNA-binding domains. Current Opinion in Genetics and Development 1994, 4:647451 Introduction mutants led eo the early notion that iUVl influences the Gte of leaf cells. Recent studies have shed light on the In higher plants, the formation and differentiation of normaI role of KNY. In localization experiments, KNl cells occurs in an orderly manner, ofien near meristems, is undetectable in leaves, but it is abundant in the api- which are groups of dividing cells chat act like permanent cal meristem and the immature axes of vegetative and stem cell populations. Cell differentiation in plants dif- floral shoots [7]. Also, the dominant Knl-N2 mutation fers horn that in animals because, for the most part, of a has been found to cause ectopic expression, such that lack of the relative cell movements that are characteristic KZVZ transcripts and KNl protein are detected in lateral of animal development. Also, the rigid plant cell wall veins of developing leaves (in addition to the normal makes the control of cell shape a critical aspect of cell accumulation in the meristem), which correlates well differentiation in plants. with the alterations in leaf cell fite and knot forma- The fate of undifferentiated plant cells is influenced pri- tion associated with Krzl mutants [7].