Biology subjects

Veenvliet, J.

Publications and source records attributed to Veenvliet, J..

3 recordsLinked to original sources

bioRxiv2026

Diversity in transcriptomics without cell types

Downstream analysis in single-cell and spatial transcriptomics is highly dependent on a sequence of upstream modeling choices. The non-canonicity of these choices presents challenges for reproducibility. In particular, measures of cellular heterogeneity and diversity do not solely reflect biological variation, but are also sensitive to parameter settings. A diversity measure that is robust to modeling choices, such as clustering resolution, is therefore desirable to improve reproducibility and interpretability. Here, we introduce scDIV, a similarity-sensitive measure of cellular diversity inspired by mathematical ideas in ecological science, which is robust to graph-based clustering parameters and remains applicable even in the absence of cell-type clusters. We use scDIV to quantitatively track the progress of tissue differentiation in both single-cell and spatial mouse development datasets and to evaluate different engineered stem-cell-based embryo models. In contrast to traditional entropy-based methods, such as the Hill number, used to quantify biodiversity, scDIV remains robust to clustering.

systems biology↗

bioRxiv2025

Reconstituting epiblast-extraembryonic endoderm interactions restores anterior-ventral patterning in stem cell-based embryo models.

During mammalian embryogenesis, reciprocal interactions between the epiblast and extraembryonic endoderm are critical for germ layer specification and body plan development during gastrulation. Gastruloids recapitulate aspects of gastrulation in the absence of extraembryonic cues, resulting in a predominantly posteriorized and dorsalized phenotype with a limited lineage diversity. Here, we establish a modular co-aggregation ("aggregoid") strategy that spatially couples embryonic and extraembryonic endoderm-like cells to reconstruct key interactions in vitro. This drives self-organized anterior-ventral patterning together with the emergence of node- and notochord-like structures, enriched endodermal populations, and increased mesodermal diversity, including cardiopharyngeal lineages and vascular endothelium. Our findings demonstrate that modular engineering of lineage interactions can direct self-organized patterning in stem-cell-based embryo models and provide a versatile framework for generating defined morphotypes.

developmental biology↗

bioRxiv2025

Tissue surface mechanics constrains proliferation-driven forces to guide mammalian body axis elongation

Mammalian embryos undergo complex morphogenetic changes after implantation in the uterus. The elongation of the body along a head-to-tail axis is a pivotal event, as it lays the foundation of the body plan. While genetic and biochemical aspects of mammalian body elongation have been uncovered, the physical mechanism of axial morphogenesis remains unknown, largely due to the inaccessibility of the implanted embryo to physical measurements and manipulations in utero. Gastruloids, a stem-cell-based embryo model of mammalian axial morphogenesis, lift such limitations. Combining live imaging, direct mechanical measurements, and chemical and mechanical perturbations, here we show that axis elongation in mouse and human gastruloids is guided by a posterior actin cap at the tissue surface that constrains the expansive forces of cell proliferation. Measurements of mechanical stresses using oil microdroplets, as well as inhibition of cell proliferation and myosin activity, show that the forces driving elongation arise from cell proliferation, and not from convergent extension movements. We find that isotropic tissue expansion is redirected into posterior elongation by the formation of a supracellular actin cap at the posterior tissue surface that restricts lateral tissue expansion. Finally, we show that posterior elongation in mouse embryos displays the key features of the physical elongation mechanism reported for mouse and human gastruloids. These findings reveal that mammalian body axis elongation, including human, occurs via a different physical mechanism from other vertebrate species.

biophysics↗