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Giesbrecht, K.

Publications and source records attributed to Giesbrecht, K..

2 recordsLinked to original sources

A Combined Computational Fluid Dynamics Modeling and Geometric Morphometrics Methods Approach to Quantifying Hemodynamic and Anatomical Features of Embryonic Chick Heart Anatomies Reconstructed from Light Sheet Fluorescence Microscopy Imaging

Although congenital heart defects occur in approximately 1% of newborns in the US annually, their pathogenesis remains largely unknown. Less than a third of congenital heart defects are traced a known genetic or environmental cause. It has been demonstrated that hemodynamic forces such as wall shear stress are critical for heart development. However, measuring these hemodynamic factors in vivo is infeasible due to physical limitations, such as the small size and constant motion of the embryonic heart. An alternative approach is to recapitulate the hemodynamic environment by simulating blood flow and calculating the resulting hemodynamic forces through computational fluid dynamics modeling. We use computational fluid dynamics modeling to quantify hemodynamics in a cohort of cell-accurate embryonic chick heart anatomies reconstructed using light sheet fluorescent microscopy. Additionally, we perform a quantitative analysis on geometric features using geometric morphometric methods. Together, the high-resolution but accessible imaging technique of light sheet fluorescence microscopy to reconstruct the anatomies paired with computational fluid dynamics modeling and geometric morphometrics methods produces a fast and accessible pipeline for quantitative hemodynamic and anatomical analysis in embryonic heart development.

developmental biology↗

Single cell transcriptomics reveals a signaling roadmap coordinating endoderm and mesoderm lineage diversification during foregut organogenesis

Visceral organs, such as the lungs, stomach, liver and pancreas, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding splanchnic mesoderm (SM). While patterning of DE lineages has been fairly well studied, paracrine signaling controlling SM regionalization and how this is coordinated with the epithelial identity during organogenesis is obscure. Here we used single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This uncovered an unexpected diversity in the SM cells that developed in close register with the organ-specific epithelium. From these data, we inferred a spatiotemporal signaling roadmap of the combinatorial endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validated key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging the signaling road map we generated different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell.

developmental biology↗