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BioE Seminar: New Genomic Technologies to Measure and Manipulate Cell Identity
Thursday, October 22, 2020 - 12:00pm to 1:00pm
Samantha Morris, Ph.D., Assistant Professor of Genetics and Developmental Biology, Washington University in St. Louis
Cell reprogramming can be achieved by ectopically expressing transcription factors (TFs) to directly induce fully-differentiated cells to adopt alternate identities, generating therapeutically useful cell types. This approach, termed 'direct lineage reprogramming' has generated an array of diverse cell identities to date. The inefficiency of reprogramming and heterogeneity of cells generated by these protocols have largely precluded mechanistic analysis. To overcome these challenges, we have developed innovative technologies to permit lineage tracing and recording of TF binding, in parallel with measurement of cell identity, at single-cell resolution. Based on our previous findings and preliminary data, we hypothesize that cells can be coaxed onto desired reprogramming trajectories from the outset of cell fate conversion via the precise manipulation of gene regulatory networks (GRNs). Our research aims to 1) Investigate broad mechanisms of cell fate reprogramming, across diverse lineage conversion protocols, leveraging our lineage tracing strategy to define reprogramming trajectories and outcomes; 2) Integrate single-cell recording of TF binding and chromatin accessibility, along reprogramming trajectories, revealing the genetic regulation characterizing these paths; 3) Direct cells toward defined and fully functional cell identities, implementing a high-resolution GRN reconstruction methodology to prioritize candidate regulatory factors to enhance reprogramming outcome.