Professor & Students

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)

Stem Cells, Inked Episode 5 (Metabolism & Cell Fate)

 
Teacher Instructing

CURENT PROJECTS

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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).

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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.

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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.

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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.

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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.

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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.

 
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LAB MEMBERS

 
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DEAN H. BETTS, PHD

Professor

BSc Honours Cell Biology, Western
MSc Zoology, Western
PhD Biomedical Sciences, Guelph
PDF Genetics, CWRU

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QUINN

Executive Assistant

PhD Best Doggo, Bett's School

Project: The lab's lab

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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

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ALEX KOZLOV

PhD Candidate (Co-supervisor Robert Cumming)


BSc Honors Biology, Western

Project: Examining the relationship between lactate and cell fate.

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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.

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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.


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VIRGINIA WOLFE

MSc Candidate

BSc Honours Physiology, McMaster University

Project: The role of p66Shc in regulating preimplantation embryo metabolism

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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

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WINNY WANG

Admin & Outreach, MA Student

BSc Biology and Political Science, Western

FEATURED PUBLICATION

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SMALL-MOLECULE INDUCTION OF CANINE EMBRYONIC STEM CELLS TOWARD NAÏVE PLURIPOTENCY

Tobias et al. Stem Cells Dev. 2016 Aug 15;25(16):1208-22.

 
Education Books Bookshelfs

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 ICKao 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. 

LOSS OF P66SHC PROMOTES PRIMITIVE ENDODERM IDENTITY IN THE INNER CELL MASS OF MOUSE BLASTOCYSTS

November 1, 2018

Edwards NA, Watson AJ, Betts DH (2018). Loss of p66Shc promotes primitive endoderm identity in the inner cell mass of mouse blastocysts. Stem Cells and Development 27(21):1479-1493.

ANALYSIS OF MITOCHONDRIAL DIMENSIONS AND CRYSTAL STRUCTURE IN PLURIPOTENT STEM CELLS USING TRANSMISSION ELECTRON MICROSCOPY

November 2018

Tobias IC, Khazaee RBetts DH (2018). Analysis of mitochondrial dimensions and crystal structure in pluripotent stem cells using transmission electron microscopy. Current Protocols in Stem Cell Biology 47(1):e67. 

https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/cpsc.67

METABOLIC PLASTICITY DURING TRANSITION TO NAÏVE-LIKE PLURIPOTENCY IN CANINE EMBRYO-DERIVED STEM CELLS

May 17, 2018

Tobias IC, Isaac RR, Dierolf J, Khazaee R, Cumming RC and Betts DH (2018). Metabolic plasticity during transition to naïve-like pluripotency in canine embryo-derived stem cells. Stem Cell Research 30:22-33. 

https://www.sciencedirect.com/science/article/pii/S1873506118301235?via%3Dihub

CD-1 MOUSE FERTILITY RAPIDLY DECLINES AND IS ACCOMPANIED WITH EARLY PREGNANCY LOSS UNDER CONVENTIONAL HOUSING CONDITIONS

March 1, 2018

Crocker K, Calder MD, Edwards NA, Betts DH, Watson AJ. CD-1 mouse fertility rapidly declines and is accompanied with early pregnancy loss under conventional housing conditions. Theriogenology. 2018 Mar 1;108:245-254.

TREATMENT WITH AICAR INHIBITS BLASTOCYST DEVELOPMENT, TROPHECTODERM DIFFERENTIATION AND TIGHT JUNCTION FORMATION AND FUNCTION IN MICE

November 1, 2017

Calder MD, Edwards NA, Betts DH, Watson AJ. Treatment with AICAR inhibits blastocyst development, trophectoderm differentiation and tight junction formation and function in mice. Mol Hum Reprod. 2017 Nov 1;23(11):771-785.

CONNEXIN43 MUTANT PATIENT-DERIVED INDUCED PLURIPOTENT STEM CELLS EXHIBIT ALTERED DIFFERENTIATION POTENTIAL

June 2016

Esseltine JL, Shao Q, Brooks C, Sampson J, Betts DH, Séguin CA, Laird DW. Connexin43 Mutant Patient-Derived Induced Pluripotent Stem Cells Exhibit Altered Differentiation Potential. J Bone Miner Res. 2017 Jun;32(6):1368-1385.

CHARACTERIZATION AND IMMUNOMODULATORY EFFECTS OF CANINE ADIPOSE TISSUE- AND BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS

December 1, 2016

Russell KA, Chow NH, Dukoff D, Gibson TW, LaMarre J, Betts DH, Koch TG. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells. PLoS One. 2016 Dec 1;11(12):e0167442.

SMALL MOLECULE INDUCTION OF CANINE EMBRYONIC STEM CELLS TOWARDS NAIVE PLURIPOTENCY

August 15, 2016

Tobias IC, Brooks CR, Teichroeb JH, Villagómez DA, Hess DA, Séguin CA, Betts DH. Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naïve Pluripotency. Stem Cells Dev. 2016 Aug 15;25(16):1208-22.

P66SHC, A KEY REGULATOR OF METABOLISM AND MITOCHONDRIAL ROS PRODUCTION, IS DYSREGULATED BY MOUSE EMBRYO CULTURE

September 2016

Edwards NA, Watson AJ, Betts DH. P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture. Mol Hum Reprod. 2016 Sep;22(9):634-47.

THE ROLE OF TELOMERES AND TELOMERASE REVERSE TRANSCRIPTASE ISOFORMS IN PLURIPOTENCY INDUCTION AND MAINTENANCE

August 2, 2016

Teichroeb JH, Kim J, Betts DH. The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance. RNA Biol. 2016 Aug 2;13(8):707-19.

CANINE PLURIPOTENT STEM CELLS: ARE THEY READY FOR CLINICAL APPLICATIONS?

October 7, 2015

Betts DH,