Dean H Betts

Dean H Betts
The University of Western Ontario | UWO · Department of Physiology and Pharmacology

PhD

About

165
Publications
18,432
Reads
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3,436
Citations
Introduction
Our current research projects: 1. Elucidating the extra-telomeric roles of telomerase splice variants. 2. Developing pluripotent stem cell technologies in the dog. 3. Redox regulation of early embryo development and during stem cell differentiation. 4. The role of premature senescence in intrauterine growth restriction (IUGR).
Additional affiliations
July 2016 - present
The University of Western Ontario
Position
  • Professor (Full)
January 2013 - present
The University of Western Ontario
Position
  • Director, Collaborative Graduate Program in Developmental Biology
January 2008 - June 2016
The University of Western Ontario
Position
  • Professor (Associate)
Education
January 2001 - December 2001
Case Western Reserve University
Field of study
  • Genetics
September 1997 - December 2000
University of Guelph
Field of study
  • Biomedical Sciences
September 1994 - April 1996
The University of Western Ontario
Field of study
  • Developmental Biology

Publications

Publications (165)
Article
Full-text available
Recent evidence points to extra-telomeric, non-canonical roles for telomerase in regulating stem cell function. In this study, human embryonic stem cells (hESCs) were cultured in 20% or 2% oxygen microenvironments for up to five days and evaluated for telomerase reverse transcriptase (TERT) expression and telomerase activity. Results showed increas...
Article
Full-text available
The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, inclu...
Article
The in vitro production of mammalian embryos suffers from low efficiency, with 50-70% of all fertilized oocytes fail to develop to the blastocyst stage. This high rate of developmental failure is due, in part, to the effects of oxidative stress generated by reactive oxygen species (ROS). The p66Shc adaptor protein controls oxidative stress response...
Article
Full-text available
Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or alternative lengthening of telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked...
Article
Full-text available
Rationale TERT, (catalytic subunit of telomerase), is linked to development of coronary artery disease (CAD); however, whether the role of nuclear vs. mitcondrial actions of TERT are involved is not determined. Dominant-negative TERT splice variants contribute to decreased mitochondrial integrity and promote elevated ROS production. We hypothesize...
Article
Cellular metabolism plays both an active and passive role in embryonic development, pluripotency, and cell-fate decisions. However, little is known regarding the role of metabolism in regulating the recently described "formative" pluripotent state. The pluripotent developmental continuum features a metabolic switch from a bivalent metabolism (both...
Article
This chapter details 3D morphological topography of colony architecture optimization and nuclear protein localization by co-immunofluorescent confocal microscopy analysis. Colocalization assessment of nuclear and cytoplasmic cell regions is detailed to demonstrate nuclear and cytoplasmic localization in mEpiSCs by confocal microscopy and orthogonal...
Article
Here we describe methodologies to characterize, delineate, and quantify pluripotent cells between naïve, formative, and primed pluripotent state mouse embryonic stem cell (mESCs) populations using flow cytometric analysis. This methodology can validate pluripotent states, sort individual cells of interest, and determine the efficiency of transition...
Article
Treatment of mouse preimplantation embryos with elevated palmitic acid (PA) reduces blastocyst development, while co-treatment with PA and oleic acid (OA) together rescues blastocyst development to control frequencies. To understand the mechanistic effects of PA and OA treatment on early mouse embryos, we investigated the effects of PA and OA, alon...
Article
Full-text available
As obese and overweight patients commonly display hyperlipidemia, and are increasingly accessing fertility clinics for their conception needs, our studies are directed at understanding the effects of hyperlipidemia on early pregnancy. We have focused on investigating palmitic acid (PA) and oleic acid (OA) treatment alone and in combination from the...
Article
Full-text available
In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medi...
Preprint
Cellular metabolism plays both an active and passive role in embryonic development, pluripotency, and cell-fate decisions. However, little is known regarding the role of metabolism in regulating the recently described formative pluripotent state. The pluripotent developmental continuum features a metabolic switch from a bivalent metabolism (both gl...
Article
Study question The aim of the study is to identify the autophagic profile and the effects of fatty acid treatments on autophagic activity in preimplantation mouse embryos. Summary answer Autophagic activity varies significantly in early stages of mouse preimplantation development; exposure to fatty acids alters the embryonic autophagy profile. Wh...
Article
Study question Our objective is determining whether supplementing embryo culture media with palmitic acid and/or oleic acid impacts Nrf2/Keap1 antioxidant response pathways during preimplantation mouse embryo development. Summary answer Supplementation of embryo culture media with palmitic acid increases cellular Nrf2 levels per embryo after 48-ho...
Article
Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of the pluripotency continuum, referred to as naïve and primed pluripotent states, respectively. These divergent pluripotent states differ in several ways including growth factor requirements, transcription factor expression, DNA methylation patterns,...
Article
Full-text available
Extracellular microRNA (miRNA) sequences derived from the pre-implantation embryo have attracted interest for their possible contributions to the ongoing embryonic–uterine milieu, as well as their potential for use as accessible biomarkers indicative of embryonic health. Spent culture media microdroplets used to culture late-stage E4.0 murine blast...
Article
Full-text available
Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further comp...
Article
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Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of the pannexin family of channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, the mechanisms responsible for coordinating and regulating PANX...
Article
Full-text available
Background Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells h...
Article
Full-text available
Induced pluripotent stem cells (iPSCs) are undifferentiated stem cells characterized by the ability to differentiate into any cell type in the body. iPSCs are a relatively new and rapidly developing technology in many fields of biology, including developmental anatomy and physiology, pathology, and toxicology. These cells have great potential in re...
Article
Elective single embryo transfer is rapidly becoming the standard of care in assisted reproductive technology for patients under the age of 35 years with a good prognosis. Clinical pregnancy rates have become increasingly dependent on the selection of a single viable embryo for transfer, and diagnostic techniques facilitating this selection continue...
Preprint
Full-text available
Background: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells...
Article
Full-text available
Obesity is associated with altered fatty acid profiles, reduced fertility, and assisted reproductive technology (ART) success. The effects of palmitic acid (PA), oleic acid (OA), and their combination on mouse preimplantation development, endoplasmic reticulum (ER) stress pathway gene expression, lipid droplet formation, and mitochondrial reactive...
Article
Full-text available
Recent evidence has emerged that cancer cells can use various metabolites as fuel sources. Restricting cultured cancer cells to sole metabolite fuel sources can promote metabolic changes leading to enhanced glycolysis or mitochondrial OXPHOS. However, the effect of metabolite-restriction on non-transformed cells remains largely unexplored. Here we...
Preprint
Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of a pluripotency continuum, referred to as naïve and primed pluripotent states, respectively. These divergent pluripotent states differ in several ways including growth factor requirements, transcription factor expression, DNA methylation patterns, a...
Preprint
Full-text available
Premature senescence in low birth weight rodents is associated with later life metabolic disease, including the development of insulin resistance. Telomerase, a reverse transcriptase enzyme with telomeric and non-telomeric functions, is present at high levels during development to maintain and repair long telomere lengths and to protect cells from...
Article
Characterization of the pluripotent "ground state" has led to a greater understanding of species-specific stem cell differences and has imparted an appreciation of the pluripotency continuum that exists in stem cells in vitro. Pluripotent stem cells are functionally coupled via connexins that serve in gap junctional intercellular communication (GJI...
Article
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Abstract A key pathological feature of Alzheimer’s disease (AD) is the accumulation of the neurotoxic amyloid beta (Aβ) peptide within the brains of affected individuals. Previous studies have shown that neuronal cells selected for resistance to Aβ toxicity display a metabolic shift from mitochondrial-dependent oxidative phosphorylation (OXPHOS) to...
Article
Dynamic alterations to mitochondrial structure and function regulate cell fate decisions and underlie multiple age‐related and genetic diseases that are modeled using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Transmission electron microscopy (TEM) can be used to obtain high‐resolution micrographs of mitochondria, but m...
Article
Full-text available
The p66Shc adaptor protein regulates apoptosis and senescence during early mammalian development. However, p66Shc expression during mouse preimplantation development is upregulated at the blastocyst stage. Our objective was to determine the biological function of p66Shc during mouse blastocyst development. Here we demonstrate that a reduced p66Shc...
Article
Full-text available
Pluripotent stem cells (PSCs) have been described in naïve or primed pluripotent states. Domestic dogs are useful translational models in regenerative medicine, but their embryonic stem cells (cESCs) remain narrowly investigated. Primed-like cESCs expanded in the presence of leukemia inhibitory factor and fibroblast growth factor 2 (LIF-FGF2) acqui...
Article
CD-1 mice are commonly employed as a research model for defining mechanisms controlling early mammalian development and for understanding environmental impacts on mammalian fertility. CD-1 female mice were kept four to eight months under conventional animal care housing, and were fed ad libitum with normal laboratory mouse chow. Female weight, mati...
Article
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Study question: What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function? Summary answer: AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur. What is known already: A...
Article
Full-text available
We present for the first time the generation of induced pluripotent stem cells (iPSCs) from a patient with a connexin-linked disease. The importance of gap junctional intercellular communication in bone homeostasis is exemplified by the autosomal dominant developmental disorder oculodentodigital dysplasia (ODDD) which is linked to mutations in the...
Article
Full-text available
Background Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the bio...
Article
Full-text available
Naïve and primed pluripotent stem cells (PSC) reflect discrete pluripotent states that approximate the inner cell mass or the progressively lineage-restricted peri-gastrulation epiblast, respectively. Cells that occupy primed pluripotency have distinct epigenetic landscapes, transcriptional circuitry and trophic requirements compared to their naïve...
Article
STUDY QUESTION Do high oxygen tension and high glucose concentrations dysregulate p66Shc (Src homologous-collagen homologue adaptor protein) expression during mouse preimplantation embryo culture? SUMMARY ANSWER Compared to mouse blastocysts in vivo, P66Shc mRNA and protein levels in blastocysts maintained in vitro increased under high oxygen tens...
Article
Telomeres are linear guanine-rich DNA structures at the ends of chromosomes. The length of telomeric DNA is actively regulated by a number of mechanisms in highly proliferative cells such as germ cells, cancer cells, and pluripotent stem cells. Telomeric DNA is synthesized by way of the ribonucleoprotein called telomerase containing a reverse trans...
Article
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The derivation of canine embryonic stem cells and generation of canine-induced pluripotent stem cells are significant achievements that have unlocked the potential for developing novel cell-based disease models, drug discovery platforms, and transplantation therapies in the dog. A progression from concept to cure in this clinically relevant compani...
Article
Rational: Heart disease is the leading cause of death worldwide and abnormalities in mitochondrial function are increasingly recognized in association with cardiomyopathy, heart failure, endothelial dysfunction and coronary artery disease (CAD). However the direct contribution and mechanism of the mitochondrial dysfunction on the development of CAD...
Article
Full-text available
Morpholino oligonucleotides (MO) are an innovative tool that provides a means for examining and modifying gene expression outcomes by antisense interaction with targeted RNA transcripts. The site-specific nature of their binding facilitates focused modulation to alter splice variant expression patterns. Here we describe the steric-blocking of human...
Article
Full-text available
The derivation of canine embryonic stem cells (cESCs) represents a significant achievement and opens the door to further stem cell research and therapies in the dog. Canines share a common environment with humans and exhibit a host of genetic diseases, many of which have human parallels. Thus, the canine model presents unique advantages over other...
Article
Full-text available
Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90...
Article
Full-text available
Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or ce...
Article
Full-text available
The cellular microenvironment comprises soluble factors, support cells, and components of the extracellular matrix (ECM) that combine to regulate cellular behavior. Pluripotent stem cells utilize interactions between support cells and soluble factors in the microenvironment to assist in the maintenance of self-renewal and the process of differentia...
Chapter
Stem cell research and its application can potentially revolutionize future therapy for many human and animal diseases by transplanting stem cell-derived specialized cells to repair or regenerate injured or diseased tissues. Stem cells are undifferentiated cells found in embryonic and/or adult tissue with the ability to self-renew and differentiate...