Cheryle A. Seguin

Assistant Professor

Cheryle Seguin

PH.D. University of Toronto
M.Sc. University of Western Ontario
B.Sc. University of Western Ontario
Office:  Dental Sciences Building, Room 0035A
Phone: (519) 661-2111 ext 82977
Fax: (519) 850-2459
Visit Dr. Seguin's Website
See Publications by Cheryle Séguin on PubMed

Human Stem Cell Lab

My studies are focused on using human embryonic stem cells to understand the mechanisms regulating early development and cell lineage specification.  Using genetic tools to induce the expression of developmentally relevant transcription factors, our studies are aimed towards the guided differentiation of human embryonic stem cells (HESC) towards lineage committed, tissue-specific progenitor cells.

1)  Generation of Pancreatic Endocrine Progenitor cells for B-cell replacement
Diabetes is a chronic disease of insulin insufficiency resulting from autoimmune destruction of pancreatic β cells (Type I), or β cell dysfunction (Type II).  While islet transplantation can restore insulin independence in diabetic patients, the shortage of donor tissues underscores the need for an alternative source of cells. Research in my lab will focus on the development of strategies to produce pancreatic islets, or fully functional β cells from human stem cells by exploiting the function of transcription factors in cell lineage commitment. Our previous studies demonstrate that SOX17 is a lineage-determining transcription factor which, when expressed in HESC, produces a stable source of proliferative definitive endoderm progenitors. We will use cells expressing an inducible form of SOX17 to identify transcription factors whose subsequent activation can promote the formation of pancreatic islet progenitor cells.  The role of the islet microenvironment in facilitating endocrine cell maturation will also be explored using three-dimensional tissue culture systems to recreate the cell-cell and cell-matrix interactions present in the developing pancreas.

2) Delineating the Role of the Notochord during Intervertebral Disc Development
Intervertebral discs form the soft connective tissue joints of the spine required for spinal stabilization, load bearing, and movement. The central part of the disc, the nucleus pulposus, plays a key role in the physiological disc function, however the developmental origin of its cells and the role of the notochord in its formation and maintenance are unknown. During development, cells of the notochord initiate the process of spine formation.  These cells persist within the fully formed intervertebral disc, and their eventual loss has been correlated with aging and degeneration. Our studies will determine the role of notochord cells at specific stages of intervertebral disc development to determine if they act as stem cells in the nucleus pulposus. To trace notochord cells in the embryo and isolate them from distinct stages of spine development, we have generated a genetically engineered mouse in which notochord cells are marked by the expression of reporter genes. Deciphering the factors that control intervertebral disc development may suggest strategies for the tissue engineering of these structures, including the differentiation of human stem cells towards a disc phenotype.

Séguin CA, Draper JS, Nagy A, Rossant J. (2008) Induction of endoderm differentiation by SOX transcription factors in human embryonic stem cells Cell Stem Cell 3:182-195.

Hotta A, Cheung AYL, Farra N, Vijayaragavan K, Séguin CA, Draper JS, Pasceri P, Maksakova IA, Mager DL, Rossant J, Bhatia M, Ellis J. (2009) Enriched isolation of reprogrammed human iPS cells using EOS lentiviral vectors to select for pluripotency (Under review Nature Methods)

Séguin CA, Pilliar R, Madri J, Kandel R. (2008) Mechanism of MT1-MMP activation by TNFa in nucleus pulposus tissue: implications for matrix degradation in intervertebral disc degeneration. Spine 33(4):356-65.

Séguin CA, Bojarski M, Pilliar R, Roughley P, Kandel R. (2006) Differential regulation of matrix degrading enzymes in a TNFa induced model of nucleus pulposus degeneration. Matrix Biology. 25: 409-418

Séguin CA, Grynpas M, Pilliar R, Waldman S, Kandel R. (2004). Tissue Engineered Nucleus Pulposus Tissue Formed on a Porous Calcium Polyphosphate Substrate. Spine. 29(12):1299-1306.

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