Van Dongen, S. | Search bioRxiv

bioRxiv2022

Multi-organ functions of yolk sac during human early development

The yolk sac (YS) represents an evolutionarily-conserved extraembryonic structure that ensures timely delivery of nutritional support and oxygen to the developing embryo. However, the YS remains ill-defined in humans. We therefore assemble a complete single cell 3D map of human YS from 3-8 post conception weeks by integrating multiomic protein and gene expression data. We reveal the YS as a site of primitive and definitive haematopoiesis including a YS-specific accelerated route to macrophage production, a source of nutritional/metabolic support and a regulator of oxygen-carrying capacity. We reconstruct the emergence of primitive haematopoietic stem and progenitor cells from YS hemogenic endothelium and their decline upon stromal support modulation as intraembryonic organs specialise to assume these functions. The YS therefore functions as three organs in one revealing a multifaceted relay of vital organismal functions as pregnancy proceeds. One Sentence SummaryHuman yolk sac is a key staging post in a relay of vital organismal functions during human pregnancy.

developmental biology↗

bioRxiv2019

MeshMonk: Open-source large-scale intensive 3D phenotyping

In the post-genomics era, an emphasis has been placed on disentangling genotype-phenotype connections so that the biological basis of complex phenotypes can be understood. However, our ability to efficiently and comprehensively characterize phenotypes lags behind our ability to characterize genomes. Here, we report a toolbox for fast and reproducible high-throughput dense phenotyping of 3D images. Given a target image, a rigid registration is first used to orient a template to the target surface, then the template is transformed further to fit the specific shape of the target using a non-rigid transformation model. As validation, we used N = 41 3D facial images registered with MeshMonk and manually landmarked at 19 locations. We demonstrate that the MeshMonk registration is accurate, with 0.62 mm as the average root mean squared error between the manual and automatic placements and no variation in landmark position or centroid size significantly attributable to landmarking method used. Though validated using 19 landmarks for comparison with traditional methods, MeshMonk allows for automatic dense phenotyping, thus facilitating more comprehensive investigations of 3D shape variation. This expansion opens up an exciting avenue of study in assessing genomic and phenomic data to better understand the genetic contributions to complex morphological traits.

evolutionary biology↗