Chelsea Kehoe
Pronouns: she/her
Research Mentor(s): Christa Ventresca
Research Mentor School/College/Department: Department of Human Genetics / Medicine
Program:
Authors: Christa Ventresca, Chelsea Kehoe, Ashna Atukuri, Usman Siddiqui, Arushi Varshney, Peter Orchard, Yao-chang Tsan, Andre Monteiro da Rocha, Markku Laakso, Jaakko Tuomilehto, Timo A. Lakka, Karen L. Mohlke, Michael Boehnke, Laura J. Scott, Heikki A. Koistinen, Francis S. Collins, Todd Herron, Stephanie Bielas, Stephen C. J. Parker
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 94
Abstract
Type 2 diabetes (T2D) is a complex disease that is impacted by a lot of different genes and the environment. Previously, 287 skeletal muscle biopsies, which attract interest due to their involvement in insulin absorption, were profiled. A genome wide association study (GWAS), which compared two sets of data, one from people with T2D, and one from people without, was also conducted. The comparison between biopsies and GWAS found that the fibro-adipogenic progenitors’ (FAPs) chromatin accessibility quantitative trait locus (caQTL), a sequence of DNA that impacts how open or closed chromatin is for transcription availability, was strongly associated with T2D GWAS signals, making them a desirable cell type to investigate. FAPs, which are a type of stem cell that can turn into muscle, bone, or fat, are involved in development, so studying them can mean potentially catching the risk of T2D earlier. From a subset of the 287 individuals, 39 induced pluripotent stem cell (iPSC) lines were gathered and now we are differentiating them into FAPs to further investigate the cell type. Differentiation is a 21 day process, where cells go through several states which involve different environments of plates and media. Through this differentiation, we aim to investigate the impact of FAP-specific molecular mechanisms such as chromatin accessibility on T2D risk and T2D-related traits. The iPSC-derived FAPs display FAP morphology, and flow cytometry has shown the loss of expression of pluripotency markers while showing the gain of FAP marker expression, which demonstrates how iPSCs can be successfully differentiated into FAPs. Currently, the experiment is being upscaled to 39 iPSC-derived FAP samples. Later, these will be used to investigate how gene expression and chromatin accessibility are impacted by different environments, high-glucose, high-insulin, and basal levels.
