11:30 - 12:00 :
(Mathematics, Ohio State University)
-Title: Spatial Dynamics of Stem Cells and Multi-Stage Cell Lineages in Tissue Stratification
In developing and self-renewing tissues, differentiated cell types are typically specified through the actions of multistage cell lineages. Such lineages commonly include a stem cell and multiple progenitor (transit amplifying; TA) cell stages, which ultimately give rise to terminally differentiated (TD) cells. Typically, as the tissue reaches a tightly controlled steady-state size, the cells at different lineage stages also assume distinct spatial locations within the tissue. Although significant genetic information are revealed on locations of different type of cells, the underlining mechanisms that cause the spatial heterogeneity are not yet completely understood. In this talk, I will present modeling and simulations to explore several plausible strategies that can be utilized to create stratification during development or regeneration of olfactory epithelium (OE) in mouse.
12:00 - 12:30 :
(Agricultural and Biological Engineering, Purdue University)
-Title: Systems biology of tissue patterning: insights from Drosophila embryos, Zebrafish embryos, and the Drosophila germarium
The spatiotemporal regulation of cell differentiation relies on numerous extracellular cues, intracellular responses, and feedback interactions between the intra- and extracellular environment. However, the classic view of morphogen-mediated patterning considers decoupled gradient formation and cell-interpretation events. To investigate the dynamic signaling landscape of cells embedded in a tissue we focused on models of stem cell regulation and early embryo development. For each unique patterning context, we developed 3D finite element models based on available image data and employed a common approach to address the following question: How does feedback between intra- and extracellular environments impact morphogen activity and patterning? To address this question in the context of stem-cell regulation by Bone Morphogenetic Proteins (BMPs), we developed a 3D model of the Drosophila germarium. We found that positive feedback that enhances ligand endocytosis leads to cell competition for limited amounts of BMP ligands and support for only 2-3 stem cells per niche, consistent with experimental observations. We extended the study to embryonic patterning by BMPs and found that positive feedback that leads to increased endocytosis capacity leads to a similar cell-competition event and autoregulation of the number of high BMP-signaling cells. In the context of developing Zebrafish embryos, positive feedback on an extracellular regulator called Sizzled autoregulates the morphogen distribution shape, ensuring robust patterning of multiple target genes. In summary, the autoregulation of morphogens by feedback provides a mechanism to ensure robust delineation of cell populations through competition and modification of gradient shape.