Biology subjects

Ehrig, S.

Publications and source records attributed to Ehrig, S..

3 recordsLinked to original sources

bioRxiv2023

Open-ST: High-resolution spatial transcriptomics in 3D

Spatial transcriptomics (ST) methods have been developed to unlock molecular mechanisms underlying tissue development, homeostasis, or disease. However, there is a need for easy-to-use, high-resolution, cost-efficient, and 3D-scalable methods. Here, we report Open-ST, a sequencing-based, open-source experimental and computational resource to address these challenges and to study the molecular organization of tissues in 3D. In mouse brain, Open-ST captured transcripts at subcellular resolution and reconstructed cell types. In primary tumor and patient-matched healthy/metastatic lymph nodes, Open-ST captured the diversity of immune, stromal and tumor populations in space. Distinct cell states were organized around cell-cell communication hotspots in the tumor, but not the metastasis. Strikingly, the 3D reconstruction and multimodal analysis of the metastatic lymph node revealed spatially contiguous structures not visible in 2D and potential biomarkers precisely at the 3D tumor/lymph node boundary. We anticipate Open-ST to accelerate the identification of spatial molecular mechanisms in 2D and 3D.

systems biology↗

bioRxiv2023

Twisted plywood-like tissue formation in vitro. Does curvature do the twist?

Little is known about the contribution of 3D surface geometry on the development of multi-layered tissues containing fibrous extracellular matrix components such as those found in bone. Here we elucidate the role of curvature in the formation of chiral, twisted plywood-like structures. Tissues consisting of murine pre-osteoblast cells (MC3T3-E1) were grown on 3D scaffolds with constant mean curvature and negative Gaussian curvature for up to 32 days. Using 3D fluorescence microscopy, the influence of surface curvature on actin stress-fiber alignment and chirality was investigated. To gain mechanistic insights, also MC3T3-E1 cells deficient in nuclear A-type lamins or treated with drugs targeting cytoskeleton proteins were used in our study. We find that wild type cells grow multilayered tissue with fibers predominantly aligned along directions of negative curvature, but where subsequent layers twist in orientation with respect to older tissues with time. Fiber orientation is conserved below the tissue surface thus creating a twisted plywood like material. We further show that this directional organization strongly depends on structural components of the cells (A-type lamins, actin and myosin). Our data indicate the importance of substrate curvature in the formation of 3D tissues and provides new insights into the emergence of chirality. Significance StatementBiological tissues (like compact bone) often consist of multiple fibrous layers which are staggered with a twisting angle relative to each other, thereby improving mechanical performance. The underlying principles of how such tissues are formed and what determines the fiber direction are still debated. Here we report the formation of a twisted plywood-like tissue grown in vitro on constant mean and negative Gaussian curvature substrates and present evidence that for tissue consisting of pre-osteoblast like cells, surface curvature is a main determinant for fiber orientation.

biophysics↗

bioRxiv2018

Surface tension determines tissue shape and growth kinetics

The growth of tissue is an essential process controlling morphogenesis and regeneration of organs [1]. In general tissue forming cells are interactive and motile [2], which can give rise to emergent physical properties such as viscous fluid behaviour as has been shown for epithelial monolayers during embryogenesis [3, 4], and for cell-agglomerates [5] with a measurable surface tension [6]. However, the mechanical integrity of tissues is provided by extracellular matrices (ECM) that turn tissues into solids with well-defined elastic properties [7]. Paradoxically, it has been shown by in-vitro experiments that even osteoid-like tissue with large amounts of ECM grows according to rules reminiscent of fluid behavior [8, 9]. Motivated by this conundrum, we show here quantitatively, by constraining growing tissues to surfaces of con ...

biophysics↗