THE BETTS LAB
Early Embryo and Pluripotent Stem Cell Laboratory
Our research program is aimed towards understanding the cellular and molecular pathways that regulate preimplantation embryo development and pluripotent stem cell function. A main focus of the lab is to train the next generation of scientists, biotechnologists and entrepreneurs.
ABOUT THE BETTS LAB
The Betts Lab utilizes unique cell and animal models including cutting-edge molecular cell biology techniques to study preimplantation embryos, stem cell function and cellular reprogramming events during early embryonic development and during the generation of induced pluripotent stem cells.
Stem Cells, Inked Episode 5 (Metabolism & Cell Fate)
CURENT PROJECTS
THE P66SHC ADAPTOR PROTEIN MAINTAINS PLURIPOTENCY AND REGULATES CELL FATE DURING EMBRYO DEVELOPMENT
CIHR submitted (PI: Betts)
The P66Shc adaptor protein belongs to the Src homology 2 domain containing (Shc) family of adaptor proteins that mediates cellular response to oxidative stress by translocating into the mitochondrial intermembrane space where it regulates metabolism and ROS production. Using established embryo-derived stem cell populations and early mouse embryo models, we will define the metabolic functions of p66Shc in regulating stem cell behavior (state) and p66Shc’s capacity to regulate stem cell differentiation into specialized cell types (fate).
REDOX REGULATION OF CANINE PLURIPOTENT STEM CELLS
NSERC Discovery (PI: Betts)
These studies will identify redox-modified proteins that will begin to elucidate the redox signaling pathways responsible for regulating self-renewal and pluripotency and will enhance our understanding of the molecular mechanisms that regulate the transition from inner cell mass (ICM) to epiblast cell fate. Modulation of the redox state during the cellular reprogramming procedure will define specific mechanisms underlying redox regulation of pluripotency induction.
EXTRA-TELOMERIC FUNCTIONS OF TELOMERASE REVERSE TRANSCRIPTASE (TERT) ISOFORMS
CIHR Operating (PI: Betts)
Expression of specific TERT isoforms likely promotes stem cell function via extra-telomeric means. These studies will elucidate the extra-telomeric roles for TERT isoforms and define new mechanisms controlling pluripotent stem cell function. These studies may reveal novel therapeutic options to enhance tissue regeneration, differentiation and repair and to treat age-related diseases such as cancer.
NON-INVASIVE IDENTIFICATION OF CONDITIONED CULTURE MEDIA CONSTITUENTS TO DETERMINE EMBRYO DEVELOPMENTAL COMPETENCE
CHRI & OB/GYN TRGF (PI: Basim Rafea)
The proposed studies are directed at characterizing microRNAs and mRNAs that are released into culture medium by preimplantation embryos. We expect to define patterns of microRNA and mRNAs that are indicative of normal preimplantation development and allow for a molecular indication of embryonic developmental competence post embryo transfer.
UNDERSTANDING AND TREATING OBESITY RELATED LOSS OF EMBRYO DEVELOPMENTAL COMPETENCE
CIHR submitted (PI: Watson)
We will investigate the possible ways in which obesity may restrict early mouse and human development by treating early mouse and human embryos with non-esterified fatty acids (NEFAs) that are sharply elevated in the serum and ovarian fluids of obese patients. We will also investigate ways in which early embryos attempt to avoid and adapt to maternal obesity effects imposed on their development. Our experiments will advance effective embryo culture medium development and will initiate approaches that could result in the production of therapeutic culture medium. Our ultimate goal is to improve the developmental capacity of early embryos and the success of assisted reproductive technologies.
SOLE FUEL SOURCE SELECTION STRATEGY TO ENHANCE PLURIPOTENCY
OIRM New Ideas Grant (PIs: Betts and Cumming)
In this project we will direct fibroblasts towards a single and/or bivalent metabolic states using sole fuel source selection to determine if their induction towards multiple pluripotent states is enhanced. Pluripotency will be assessed using various molecular markers of general, naïve, and primed pluripotency, while interrogation of metabolic pathways will be carried out by metabolic measurements and assessing various markers of glycolysis and OXPHOS. These studies will develop a simple and reliable culture protocol to modulate the bioenergetic state of somatic cells to efficiently generate high quality naïve human iPSCs for future stem cell therapies.
LAB MEMBERS
DEAN H. BETTS, PHD
Professor
BSc Honours Cell Biology, Western
MSc Zoology, Western
PhD Biomedical Sciences, Guelph
PDF Genetics, CWRU
QUINN
Executive Assistant
PhD Best Doggo, Bett's School
Project: The lab's lab
ZULEIKA C. L. LEUNG
Research Assistant
BMSc Interdisciplinary Medical Sciences, Western
MSc Physiology and Pharmacology & Developmental Biology, Western
Project: The impact of free fatty acids on preimplantation embryo autophagy
ALEX KOZLOV
PhD Candidate (Co-supervisor Robert Cumming)
BSc Honors Biology, Western
Project: Examining the relationship between lactate and cell fate.
DAVID HAWKE
PhD Candidate
BSc Chemical Engineering, Queen's
MASc Chemical Engineering, Queen's
Project: Exosome-derived miRNAs as non-invasive predictors of preimplantation embryo competence.
ANDREW POWELL
PhD Candidate (Co-supervisor Robert Cumming)
BASc Engineering Chemistry, Queen's
MASc Chemical Engineering, Queen's
Project: The role of p66Shc in neural stem cell maintenance and differentiation.
VIRGINIA WOLFE
MSc Candidate
BSc Honours Physiology, McMaster University
Project: The role of p66Shc in regulating preimplantation embryo metabolism
STEFAN GRAHOVAC
MSc Candidate
BSc Honours Specialization Biology, Western
Project: Genome-wide CRISPR-Cas9 screen to discover novel functional interactions of the p66Shc adaptor protein in regulating pluripotency
WINNY WANG
Admin & Outreach, MA Student
BSc Biology and Political Science, Western
PUBLICATIONS
EVALUATING AUTOPHAGY IN PREIMPLANTATION EMBRYOS
July 21, 2022
Leung ZCL, Hunter H, Abu Rafea B, Watson AJ, and Betts DH (2022). Evaluating Autophagy in Preimplantation Embryos. Autophagy Reports 1(1): 309-337.
MODULATION OF PKM1/2 LEVELS BY STERIC BLOCKING MORPHOLINOS ALTERS THE METABOLIC AND PLURIPOTENT STATE OF MURINE PLURIPOTENT STEM CELLS
June 8, 2022
Dierolf JG, Hunter HLM, Watson AJ, Betts DH (2022). Modulation of PKM1/2 levels by steric blocking morpholinos alters the metabolic and pluripotent state of murine pluripotent stem cells. Stem Cells and Development 31 (11-12): 278-295.
FREE FATTY ACID TREATMENT OF MOUSE PREIMPLANTATION EMBRYOS DEMONSTRATES CONTRASTING EFFECTS OF PALMITIC ACID AND OLEIC ACID ON AUTOPHAGY
May 1, 2022
Leung ZCL, Calder MD, Abu-Rafea B, Watson AJ, Betts DH (2022). Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy. Am J Physiol Cell Physiol. 322(5): C833-C848.
THE EFFECTS OF OBESITY AND NON-ESTERIFIED FATTY ACIDS ON PREIMPLANTATION EMBRYO DEVELOPMENT
2022
Leung ZCL, Betts DH, Watson AJ (2022). The effects of obesity and non-esterified fatty acids on preimplantation embryo development. Trends Dev Biol 14: 19-31.
3D IMMUNOFLUORESCENT IMAGE COLOCALIZATION QUANTIFICATION IN MOUSE EPIBLAST STEM CELLS
April 29, 2022
Dierolf JG, Watson AJ, Betts DH (2022). 3D immunofluorescent image colocalization quantification in mouse epiblast stem cells. Methods in Molecular Biology 2490: 69-79.
FLOW CYTOMETRIC CHARACTERIZATION OF PLURIPOTENT CELL PROTEIN MARKERS IN NAÏVE, FORMATIVE, AND PRIMED PLURIPOTENT STEM CELLS
April 29, 2022
Dierolf JG, Chadwick K, Brooks CR, Watson AJ, Betts DH (2022). Flow Cytometric Characterization of Pluripotent Cell Protein Markers in Naïve, Formative, and Primed Pluripotent Stem Cells. Methods in Molecular Biology 2490: 81-92.
EFFECTS OF PALMITIC ACID ON LOCALIZATION OF EMBRYO CELL FATE AND BLASTOCYST FORMATION GENE PRODUCTS
February 14, 2022
Calder MD, Chen R, MacDonald A, MacNeily Z, Leung ZCL, Adus A, Cui S, Betts DH, Abu-Rafea B, and Watson AJ (2022). Effects of palmitic acid on localization of embryo cell fate and blastocyst formation gene products. Reproduction 163(3): 133-143.
CELL THERAPY IN VETERINARY MEDICINE AS A PROOF-OF CONCEPT FOR HUMAN THERAPIES: PERSPECTIVES FROM THE NORTH AMERICAN VETERINARY MEDICINE ASSOCIATION
November 30, 2021
Arzi B, Webb TL, Koch TG, Volk SW, Betts DH, Watts A, Goodrich L, Kallos MS, Kol A (2021). Cell Therapy in Veterinary medicine as a Proof-of Concept for Human Therapies: Perspectives from the North American Veterinary Medicine Association. Front. Vet. Sci. doi: 10.3389/fvets.2021.779109.
DIFFERENTIAL LOCALIZATION PATTERNS OF PYRUVATE KINASE ISOFORMS IN MURINE NAÏVE, FORMATIVE AND PRIMED PLURIPOTENT STATES
June 26, 2021
Dierolf JG, Watson AJ, Betts DH (2021). Differential localization patterns of pyruvate kinase isoforms in murine naïve, formative and primed pluripotent states. Experimental Cell Research 405(2):112714.
MURINE BLASTOCYSTS RELEASE MATURE MICRORNAS INTO CULTURE MEDIA THAT REFLECT DEVELOPMENTAL STATUS
May 28, 2021
Hawke DC, Watson AJ, Betts DH (2021). Murine blastocysts release mature microRNAs into culture media that reflect developmental status. Frontiers in Genetics 12:655882.
ANALYSIS OF TERT ISOFORMS ACROSS TCGA, GTEX AND CCLE DATASETS
April 13, 2021
Subasri M, Shooshtari P, Watson AJ, Betts DH (2021). Analysis of TERT Isoforms Across TCGA, GTEx and CCLE Datasets. Cancers 13(8):1853.
PANNEXIN 1 BINDS Β-CATENIN TO MODULATE MELANOMA CELL GROWTH AND METABOLISM
February 26, 2021
Sayedyahossein S, Huang K, Li Z, Zhang C, Kozlov AM, Johnston D, Nouri-Nejad D, Dagnino L, Betts DH, Sacks DB and Penuela S (2021). Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism. J Biol Chem 296:100478.
EXTRACELLULAR VESICLES, MICRORNA AND THE PREIMPLANTATION EMBRYO: NON-INVASIVE CLUES OF EMBRYO WELL-BEING
January 1, 2021
Hawke DC, Watson AJ, Betts DH (2021). Extracellular Vesicles, MicroRNA and the Preimplantation Embryo: Non-Invasive Clues of Embryo Well-Being. Reproductive BioMedicine Online 41(1): 39-54.
TARGETED EXPRESSION PROFILING REVEALS DISTINCT STAGES OF EARLY CANINE FIBROBLAST REPROGRAMMING ARE REGULATED BY 2-OXOGLUTARATE HYDROXYLASES
December 9, 2020
Tobias IC, Kao MC, Parmentier T, Hunter H, LaMarre J and Betts DH (2020). Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases. Stem Cell Res Ther 11(1):528.
THE USE OF INDUCED PLURIPOTENT STEM CELLS IN DOMESTIC ANIMALS: A NARRATIVE REVIEW
December 8, 2020
Scarfone RA, Pena SM, Russell KA, Betts DH and Koch TG (2020). The Use of Induced Pluripotent Stem Cells in Domestic Animals: A Narrative Review. BMC Veterinary Research 16(1):477.
OLEIC ACID COUNTERS IMPAIRED BLASTOCYST DEVELOPMENT INDUCED BY PALMITIC ACID DURING MOUSE PREIMPLANTATION DEVELOPMENT: UNDERSTANDING OBESITY RELATED DECLINES IN FERTILITY
June 10, 2020
Yousif MD, Calder MD, Du JT, Ruetz KN, Crocker K, Urquhart BL, Betts DH, Rafea BA, Watson AJ (2020). Oleic Acid Counters Impaired Blastocyst Development Induced by Palmitic Acid during Mouse Preimplantation Development: Understanding Obesity Related Declines in Fertility. Reproductive Sciences 27(11):2038-2051.
LACTATE PRECONDITIONING PROMOTES A HIF-1-ALPHA-MEDIATED METABOLIC SHIFT FROM OXPHOS TO GLYCOLYSIS IN NORMAL HUMAN DIPLOID FIBROBLASTS
May 20, 2020
Kozlov AM, Lone A, Betts DH*, Cumming RC* (2020). Lactate preconditioning promotes a HIF-1-alpha-mediated metabolic shift from OXPHOS to glycolysis in normal human diploid fibroblasts. Scientific Reports 10: 8388. *Co-senior authors.
DYNAMIC REGULATION OF CONNEXINS IN STEM CELL PLURIPOTENCY
October 28, 2019
Esseltine JL, Brooks C, Edwards NA, Subasri M, Sampson J, Seguin C, Betts DH and Laird DW (2020). Dynamic regulation of connexins in stem cell pluripotency. Stem Cells 38(1):52-66.
TRAPPING AND SERS IDENTIFICATION OF EXTRACELLULAR VESICLES USING NANOHOLE ARRAYS.
March 7, 2019
Kaufman LH, Cooper T, Wallace GQ, Hawke DC, Betts D, Hess D, Lagugné-Labarthet F (2019). Trapping and SERS identification of extracellular vesicles using nanohole arrays. Proc. SPIE 10894, Plasmonics in Biology and Medicine XVI, 108940B.
P66SHC ACTIVATION PROMOTES INCREASED OXIDATIVE PHOSPHORYLATION AND RENDERS CNS CELLS MORE VULNERABLE TO AMYLOID BETA TOXICITY
November 20, 2018
Lone A, Harris R, Singh O, Betts DH, Cumming RC. (2018). p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity. Scientific Reports 8(1):17081.