Speaker: Clyde Campbell, adjunct assistant professor in the Department of Genetics, Development and Cell Biology at Iowa State University

Title: Induced lineage conversion across germ layers in vivo: Exploring the boundaries of cellular plasticity

Abstract: An outstanding question in the field of in vivo cellular reprogramming is to what extent can differentiated cells, while remaining in their native microenvironment, be reprogrammed to assume a different identity. Although it has been demonstrated that differentiated cells possess a certain level of plasticity in vivo, the ability to reprogram a cell to adopt the identity of a cell derived from another germ layer has eluded the field. If achievable, it would have tremendous biomedical implications in the context of regenerative medicine, by facilitating the targeting of abundant non-vital cells to regenerate lost or damaged cell types. To investigate in vivo cell lineage plasticity, we utilized the zebrafish model as a platform to determine whether differentiated vertebrate cells can be coaxed to adopt unrelated lineage identities. We found that ectopic co-expression of sox32 and oct4 in non-endoderm lineages, including skeletal muscle, were able to cell-autonomously trigger an endoderm genetic program. These endoderm-like muscle cells displayed a dramatic loss of muscle specific genes and muscle-like morphology, while upregulated key organogenesis factors, such as the pancreatic markers hnf1b and ptf1a. In addition, when exposed to a loss of Fgf signaling, these endoderm-like cells still progressed through an early endoderm genetic program, but failed to induce late pancreatic specification genes such as ptf1a. This suggests that in vivo lineage conversion of mesoderm-derived cells to endoderm-like cells requires the same molecular cues as the native endoderm. Together, our work demonstrates for the first time that differentiation across germ layers without undergoing pluripotency is achievable in vivo. This surprising finding suggests that differentiated cells in vivo are more amenable for lineage conversion than previously assumed, and this discovery may pave the way towards a new in vivo supply of cells for degenerative diseases such as diabetes.

Host: Steve Howell

Please join us for refreshments before the seminar outside Room 1414 of the Molecular Biology Building.