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When Stem Cells Grow Old: Phenotypes and Mechanisms of Stem Cell Aging Michael B
© 2016. Published by The Company of Biologists Ltd | Development (2016) 143, 3-14 doi:10.1242/dev.130633 REVIEW When stem cells grow old: phenotypes and mechanisms of stem cell aging Michael B. Schultz and David A. Sinclair* ABSTRACT Thus, a stark collapse of the hematological system does not occur All multicellular organisms undergo a decline in tissue and organ during normal aging. However, when murine HSCs with long-term + − function as they age. An attractive theory is that a loss in stem cell repopulating ability were isolated by selecting for c-Kit , lineage + number and/or activity over time causes this decline. In accordance (multiple markers), Sca-1 cells (KLS) (Ikuta and Weissman, 1992; with this theory, aging phenotypes have been described for stem cells Spangrude et al., 1988), the number of HSCs was found to steadily of multiple tissues, including those of the hematopoietic system, increase with age (de Haan et al., 1997; Morrison et al., 1996). Only intestine, muscle, brain, skin and germline. Here, we discuss recent when function was measured on a per-cell basis were old advances in our understanding of why adult stem cells age and how immunophenotypic HSCs shown to have a greatly reduced ability this aging impacts diseases and lifespan. With this increased to engraft and properly differentiate in new hosts (Dykstra et al., understanding, it is feasible to design and test interventions that 2011; Liang et al., 2005; Morrison et al., 1996). Furthermore, in delay stem cell aging and improve both health and lifespan. both mice and humans, the proportion of differentiated blood cells arising from just a few HSC clones increases, suggesting that the KEY WORDS: Age-related diseases, Hematopoietic stem cells, number of active, functional HSCs declines with age (Beerman Multicellular organisms et al., 2010; Genovese et al., 2014; Jaiswal et al., 2014). -
Focus on Stem Cells Germ Cells from Mouse and Human Embryonic Stem Cells
REPRODUCTIONREVIEW Focus on Stem Cells Germ cells from mouse and human embryonic stem cells Behrouz Aflatoonian and Harry Moore Centre for Stem Cell Biology, University of Sheffield, Sheffield S10 2UH, UK Correspondence should be addressed to H Moore; Email: [email protected] Abstract Mammalian gametes are derived from a founder population of primordial germ cells (PGCs) that are determined early in embryogenesis and set aside for unique development. Understanding the mechanisms of PGC determination and differentiation is important for elucidating causes of infertility and how endocrine disrupting chemicals may potentially increase susceptibility to congenital reproductive abnormalities and conditions such as testicular cancer in adulthood (testicular dysgenesis syndrome). Primordial germ cells are closely related to embryonic stem cells (ESCs) and embryonic germ (EG) cells and comparisons between these cell types are providing new information about pluripotency and epigenetic processes. Murine ESCs can differentiate to PGCs, gametes and even blastocysts – recently live mouse pups were born from sperm generated from mESCs. Although investigations are still preliminary, human embryonic stem cells (hESCs) apparently display a similar developmental capacity to generate PGCs and immature gametes. Exactly how such gamete-like cells are generated during stem cell culture remains unclear especially as in vitro conditions are ill-defined. The findings are discussed in relation to the mechanisms of human PGC and gamete development and the biotechnology of hESCs and hEG cells. Reproduction (2006) 132 699–707 Introduction indicate that human embryonic stem cells (hESCs) most likely display a similar developmental capacity (Clark Detailed investigations of the earliest stages of germ cell et al. -
Insights from Male Germ Cell Differentiation
Cell Death & Differentiation (2021) 28:2296–2299 https://doi.org/10.1038/s41418-021-00812-0 COMMENT Natural selection at the cellular level: insights from male germ cell differentiation 1 1 Daniel H. Nguyen ● Diana J. Laird Received: 9 February 2021 / Revised: 20 May 2021 / Accepted: 20 May 2021 / Published online: 2 June 2021 © The Author(s) 2021. This article is published with open access Waddington’s concept of differentiation as an epigenetic The germline is a fascinating context for investigating landscape provides an enduring metaphor visualizing the the consequences of heterogeneity on differentiation and options faced by stem and progenitor cells. However, cell fate. As fetal germ cells establish the gametes, their increasing understanding of cellular heterogeneity poses population dynamics can greatly influence inheritance. The new questions about the identities and behaviors of the cells conflict between diversity and orderly differentiation looms beginning this process. We now recognize a greater diver- centrally over germline development. In mouse embryos, sity of initial states for individual progenitor cells, which germ cells undertake an epic journey, from specification may affect their trajectories and disrupt progress entirely. through sex differentiation, replete with opportunities for 1234567890();,: 1234567890();,: Here, we consider how developmental selection occurs heterogeneity to develop and be assessed. Notably, an when heterogeneity in differentiating progenitors produces excess of germ cells is produced and then pruned by pro- divergent cellular outcomes of survival versus elimination. grammed cell death [5]. This occurs across diverse species Heterogeneity is a fundamental property of biological regardless of sex, suggesting that differential fitness and systems. Individual cell properties like location or cell cycle elimination are critical. -
This Thesis Has Been Submitted in Fulfilment of the Requirements for a Postgraduate Degree (E.G
This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Isolation, Characterisation and In Vitro Potential of Oogonial Stem Cells Cheryl Elizabeth Dunlop BSc Med Sci (Hons), University of Edinburgh MBChB (Hons), University of Edinburgh Doctor of Philosophy (PhD) – The University of Edinburgh – 2016 Declaration This thesis has been composed by myself and the research described herein is my own, except where work by others has been duly acknowledged. The work described in this thesis has not been submitted for any other degree or professional qualification. Cheryl Dunlop 2016 i Abstract The longstanding belief that women are born with a finite ovarian reserve has been debated for over a decade, ever since the discovery, and subsequent isolation, of purported oogonial stem cells (OSCs) from adult mammalian ovaries. This rare cell population has now been reported in the mouse, rat, pig, rhesus macaque monkey and humans and, although a physiological role for the cells has not been proven, they do appear to generate oocytes when cultured in specific environments, resulting in live offspring in rodents. -
WO 2013/002880 Al O O© O
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/002880 Al 3 January 2013 (03.01.2013) P O P C T (51) International Patent Classification: (74) Agents: LAURO, Peter C. et al; Edwards Wildman C12N 5/00 (2006.01) C12N 5/075 (2010.01) Palmer LLP, P.O. Box 55874, Boston, MA 02205 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2012/033672 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (22) Date: International Filing CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, 13 April 2012 (13.04.2012) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (25) Filing Language: English HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (26) Publication Language: English MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (30) Priority Data: OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, 61/502,840 29 June 201 1 (29.06.201 1) US SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 61/600,529 17 February 2012 (17.02.2012) US TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicants (for all designated States except US): THE (84) Designated States (unless otherwise indicated, for every GENERAL HOSPITAL CORPORATION [US/US]; 55 kind of regional protection available): ARIPO (BW, GH, Fruit Street, Boston, MA 021 14 (US). -
Germ-Line Immortality
COMMENTARY Germ-line immortality Martin M. Matzuk* Departments of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, and Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030 ajor advances in stem cell Table 1. Pathway of differentiation in males research have occurred over Spermatogonial Differentiated the last decades. Progress Markers ES cells ¡ PGCs ¡ Gonocytes ¡ stem cells ¡ spermatogonia has included the generation Mof lines of human and mouse embryonic Kit ϩϩϩ͞– – (low) ϩ ϩ ϩϩ stem (ES) cells and the identification and Thy-1 ? (low) – Oct4 ϩϩ ϩ ϩ – purification of stem cells for multiple Plzf ϩ (low)* ϩ* ϩϩ – independent lineages. Recent studies by GCNA1 – ϩ† ϩϩ ϩ Brinster and colleagues in this issue of TNAP ϩ (high) ϩ (high) – ϩ (low)͞–– PNAS (1) also suggest that the reproduc- RET ϩ (low)* ? ? ϩ – ␣ ϩ ϩ tive potential of an organism can be pro- GFR 1 (low)* ? ? (low) – NCAM ϩ ? ϩϩ ? longed indefinitely by using germ-line stem cells. It even appears that eggs and Markers that are known to be expressed (ϩ) or absent (–) in many of the pathway cells are listed. GCNA1, sperm can develop from cultured mouse germ cell nuclear antigen 1; TNAP, tissue-nonspecific alkaline phosphatase; NCAM, neural cell adhesion ES cells (2–4). Although gametes derived molecule. in vitro have yet to prove their develop- *mRNA levels. † mental potential, these studies suggest Postmigratory PGCs only. that ES cells and germ-line stem cells share many characteristics. ent males. The process was surprisingly KitϪ Sca-IϪ ␣6-integrinϩ ␣v-integrinϪ/dim In most mammalian females, meiosis efficient, with up to 100% of the injected (9, 10). -
The Effects of Dexamethasone on the Differentiation and the Fertilisation of the Germinal Primordium in the Chick Embryo Danièle Cuminge, Julian Smith, Régis Dubois
The effects of dexamethasone on the differentiation and the fertilisation of the germinal primordium in the chick embryo Danièle Cuminge, Julian Smith, Régis Dubois To cite this version: Danièle Cuminge, Julian Smith, Régis Dubois. The effects of dexamethasone on the differentiation and the fertilisation of the germinal primordium in the chick embryo. Reproduction Nutrition Devel- opment, EDP Sciences, 2000, 40 (2), pp.127-148. 10.1051/rnd:2000125. hal-00900392 HAL Id: hal-00900392 https://hal.archives-ouvertes.fr/hal-00900392 Submitted on 1 Jan 2000 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Reprod. Nutr. Dev. 40 (2000) 127–148 127 © INRA, EDP Sciences Original article The effects of dexamethasone on the differentiation and the fertilisation of the germinal primordium in the chick embryo Danièle CUMINGEa, Julian SMITHb, Régis DUBOISa* a Institut d’Embryologie Cellulaire et Moléculaire, 49 bis avenue de la Belle Gabrielle, Collège de France et CNRS, 94736 Nogent-sur-Marne Cedex, France b Centre de Biologie du Développement, Université Paul Sabatier, 31062 Toulouse, France (Received 15 December 1999; accepted 24 February 2000) Abstract — We showed that, in the chick embryo, the fertilisation of the attractive germinal epithe- lium by primary germ cells can be represented by a three-dimensional diagram in which the space and time co-ordinates are graduated in terms of the segmentation of the axial and paraxial mesoderm. -
REVIEW Hormonal Regulation of Male Germ Cell Development
117 REVIEW Hormonal regulation of male germ cell development Saleela M Ruwanpura, Robert I McLachlan and Sarah J Meachem Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168, Australia (Correspondence should be addressed to S J Meachem; Email: [email protected]) Abstract Over the past five decades, intense research using various been established that testosterone is essential for spermato- animal models, innovative technologies notably genetically genesis, and also FSH plays a valuable role. Therefore modified mice and wider use of stereological methods, unique understanding the basic mechanisms by which hormones agents to modulate hormones, genomic and proteomic govern germ cell progression are important steps towards techniques, have identified the cellular sites of spermato- improved understating of fertility regulation in health diseases. genesis, that are regulated by FSH and testosterone. It has Journal of Endocrinology (2010) 205, 117–131 Introduction (termed spermiation) requires both testosterone and FSH (reviewed in McLachlan et al. (2002a)). In humans, sperma- The past decade has been a critical period in our discoveries of togonial development, meiosis, and spermiation are the how the complex process of spermatogenic cell development three main processes that are regulated by gonadotrophins is regulated. These discoveries have been aided through the (McLachlan et al. 2002b, Matthiesson et al. 2005, 2006). use of innovative technologies, most notably genetically A stable germ cell population is determined by the modified mice, the wider use of best practice stereological balance of death (apoptosis) and division, which are influenced methods that allow the rigorous mapping of cell populations, by many biochemical factors. The highly coordinated nature unique agents to modulate hormones, and the genomic and of spermatogenesis requires intimate functional and junctional proteomic revolution. -
Disruption of Imprinting in Cloned Mouse Fetuses from Embryonic Stem
REPRODUCTIONRESEARCH Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age Caroline Maria Christante1,2, Sebastia˜o Roberto Taboga1,2, Maria Etelvina Pinto-Fochi1 and Rejane Maira Go´es1,2 1Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Sa˜o Paulo State University, IBILCE/UNESP, Rua Cristo´va˜o Colombo, 2265, CEP 15054-000 Sa˜o Jose´ do Rio Preto, Sa˜o Paulo, Brazil and 2Department of Structural and Functional Biology, State University of Campinas, UNICAMP, 13083-970 Campinas, Sa˜o Paulo, Brazil Correspondence should be addressed to R M Go´es at Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Sa˜o Paulo State University, IBILCE/UNESP; Email: [email protected] Abstract In this study, we evaluated whether maternal obesity (MO) affects testis development and gonocyte differentiation in the rat from 0.5 to 14.5 postnatal days. Male Wistar rats were used at 0.5, 4.5, 7.5, and 14.5 days post partum (dpp). These rats were born from obese mothers, previously fed with a high-fat diet (20% saturated fat), for 15 weeks, or normal mothers that had received a balanced murine diet (4% lipids). MO did not affect testis weight or histology at birth but changed the migratory behavior of gonocytes. The density of relocated cells was higher in MO pups at 0.5 dpp, decreased at 4.5 dpp, and differed from those of control pups, where density increased exponentially from 0.5 to 7.5 dpp. The numerical density of gonocytes within seminiferous cords did not vary in MO, in relation to control neonates, for any age considered, but the testis weight was 50% lower at 4.5 dpp. -
Review Article Physiologic Course of Female Reproductive Function: a Molecular Look Into the Prologue of Life
Hindawi Publishing Corporation Journal of Pregnancy Volume 2015, Article ID 715735, 21 pages http://dx.doi.org/10.1155/2015/715735 Review Article Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life Joselyn Rojas, Mervin Chávez-Castillo, Luis Carlos Olivar, María Calvo, José Mejías, Milagros Rojas, Jessenia Morillo, and Valmore Bermúdez Endocrine-Metabolic Research Center, “Dr. Felix´ Gomez”,´ Faculty of Medicine, University of Zulia, Maracaibo 4004, Zulia, Venezuela Correspondence should be addressed to Joselyn Rojas; [email protected] Received 6 September 2015; Accepted 29 October 2015 Academic Editor: Sam Mesiano Copyright © 2015 Joselyn Rojas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The genetic, endocrine, and metabolic mechanisms underlying female reproduction are numerous and sophisticated, displaying complex functional evolution throughout a woman’s lifetime. This vital course may be systematized in three subsequent stages: prenatal development of ovaries and germ cells up until in utero arrest of follicular growth and the ensuing interim suspension of gonadal function; onset of reproductive maturity through puberty, with reinitiation of both gonadal and adrenal activity; and adult functionality of the ovarian cycle which permits ovulation, a key event in female fertility, and dictates concurrent modifications in the endometrium and other ovarian hormone-sensitive tissues. Indeed, the ultimate goal of this physiologic progression is to achieve ovulation and offer an adequate environment for the installation of gestation, the consummation of female fertility. Strict regulation of these processes is important, as disruptions at any point in this evolution may equate a myriad of endocrine- metabolic disturbances for women and adverse consequences on offspring both during pregnancy and postpartum. -
Regulation of Meiotic Entry and Gonadal Sex Differentiation in the Human: Normal and Disrupted Signaling
BioMol Concepts 2014; 5(4): 331–341 Review Anne Jørgensen* and Ewa Rajpert-De Meyts Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling Abstract: Meiosis is a unique type of cell division that is DOI 10.1515/bmc-2014-0014 performed only by germ cells to form haploid gametes. Received May 1, 2014; accepted May 28, 2014 The switch from mitosis to meiosis exhibits a distinct sex-specific difference in timing, with female germ cells entering meiosis during fetal development and male germ cells at puberty when spermatogenesis is initiated. Dur- Introduction ing early fetal development, bipotential primordial germ The mitotic-meiotic switch is a unique feature of germ cells migrate to the forming gonad where they remain cell development and is one of the first manifestations of sexually indifferent until the sex-specific differentiation of sex differentiation in the developing gonad. The current germ cells is initiated by cues from the somatic cells. This understanding of the molecular mechanisms of germ irreversible step in gonadal sex differentiation involves cell differentiation and regulation of meiosis is primarily the initiation of meiosis in fetal ovaries and prevention derived from studies in mice (1–4), with only few experi- of meiosis in the germ cells of fetal testes. During the last mental studies conducted on human fetal gonads thus decade, major advances in the understanding of meiosis far (5, 6). In contrast, the physiological manifestations of regulation have been accomplished, with the discovery sex differentiation that take place in humans during fetal of retinoic acid as an inducer of meiosis being the most gonad development and the expression pattern of key prominent finding. -
Open Hester Dissertation W Appendix.Pdf
The Pennsylvania State University The Graduate School Intercollege Graduate Degree Program in Physiology THE IMPACT OF ZINC DEFICIENCY DURING OOGENESIS, FOLLICLE ASSEMBLY, AND GROWTH A Dissertation in Integrative and Biomedical Physiology by James M. Hester 2018 James Hester Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2018 ii The dissertation of James Hester was reviewed and approved* by the following: Francisco J. Diaz Associate Professor of Reproductive Biology Dissertation Advisor Chair of Committee Wendy Hanna-Rose Associate Professor and Department Head Biochemistry and Molecular Biology Alan L. Johnson Walther H. Ott Professor in Avian Biology Claire M. Thomas Associate Professor of Biology and Biochemistry and Molecular Biology Donna H. Korzick Professor of Physiology and Kinesiology Chair, Intercollege Graduate Degree Program in Physiology *Signatures are on file in the Graduate School iii ABSTRACT The ovarian follicle is the fundamental unit of the ovary and of female reproduction in mammals. Each follicle contains one oocyte enclosed in somatic cells and follicle number is determined during fetal development in humans. Growth and development of ovarian follicles (folliculogenesis) is necessary to produce viable gametes as well as ovarian hormones including estrogen and progesterone. Folliculogenesis begins in the fetal ovary and may span several decades of life. Environmental and nutritional factors that affect folliculogenesis have the potential to impact health and fertility, and may be a source of new biotechnological innovation. One such factor, zinc, has previously been found to impact the final stages of follicle development including meiotic division, ovulation, epigenetic modification, fertilization, and embryo development. However, the role of zinc during the early stages of folliculogenesis have not been evaluated.