Biology subjects

Korswagen, H. C.

Publications and source records attributed to Korswagen, H. C..

4 recordsLinked to original sources

bioRxiv2024

Systemic coordination of whole-body tissue remodeling in sea anemone local regeneration

The complexity of regeneration extends beyond local wound responses (1,2), eliciting systemic processes that engage the entire organism. However, their functional relevance, and the spatial and temporal orchestration of the underlying molecular processes distant from the injury site remain unknown. Here, we demonstrate that local regeneration in the cnidarian Nematostella vectensis involves a systemic homeostatic response, leading to coordinated whole-body remodeling. Leveraging spatial transcriptomics, endogenous protein tagging, and live imaging, we comprehensively dissect this systemic response at the organismal scale. We identify proteolysis as a critical process driven by both local and systemic upregulation of metalloproteases. We show that metalloproteinase expression levels and activity scale with the extent of tissue loss, leading to proportional long-range movement of tissue and its associated extracellular matrix. Our findings illuminate the adaptive nature of the systematic response in regeneration. We propose that this integrated regenerative mechanism, shifting the system from a steady to a dynamic homeostatic state, allows the organism to cope with a wide range of injuries.

developmental biology↗

bioRxiv2021

Endomitosis controls tissue-specific gene expression during development

Polyploid cells contain more than two copies of the genome and are found in many plant and animal tissues. Different types of polyploidy exist, in which the genome is confined to either one nucleus (mononucleation) or two or more nuclei (multinucleation). Despite the widespread occurrence of polyploidy, the functional significance of different types of polyploidy are largely unknown. Here, we assess the function of multinucleation in C. elegans intestinal cells through specific inhibition of binucleation without altering genome ploidy. Through single worm RNA sequencing, we find that binucleation is important for tissuespecific gene expression, most prominently for genes that show a rapid upregulation at the transition from larval development to adulthood. Regulated genes include vitellogenins, which encode yolk proteins that facilitate nutrient transport to the germline. We find that reduced expression of vitellogenins in mononucleated intestinal cells leads to progeny with developmental delays and reduced fitness. Together, our results show that binucleation facilitates rapid upregulation of intestine-specific gene expression during development, independently of genome ploidy, underscoring the importance of spatial genome organization for polyploid cell function.

cell biology↗

bioRxiv2020

Functional modules from variable genes: Leveraging percolation to analyze noisy, high-dimensional data

While measurement advances now allow extensive surveys of gene activity (large numbers of genes across many samples), interpretation of these data is often confounded by noise — expression counts can differ strongly across samples due to variation of both biological and experimental origin. Complimentary to perturbation approaches, we extract functionally related groups of genes by analyzing the standing variation within a sampled population. To distinguish biologically meaningful patterns from uninterpretable noise, we focus on correlated variation and develop a novel density-based clustering approach that takes advantage of a percolation transition generically arising in random, uncorrelated data. We apply our approach to two contrasting RNA sequencing data sets that sample individual variation — across single cells of fission yeast and whole animals of C. elegans worms — and demonstrate robust applicability and versatility in revealing correlated gene clusters of diverse biological origin, including cell cycle phase, development/reproduction, tissue-specific functions, and feeding history. Our technique exploits generic features of noisy high-dimensional data and is applicable, beyond gene expression, to feature-rich data that sample population-level variability in the presence of noise.Significance Statement Gene expression largely determines the fate of each cell and ultimately the development and behavior of the whole organism. Whereas most of our knowledge on gene regulatory networks has been obtained from perturbation experiments (e.g. manipulating environmental conditions, genotype, or other physiological variables), here we develop an alternative approach based on the analysis of naturally occurring variations across individuals within a population. Using both single-cell and whole-animal RNA sequencing data, we demonstrate how a rich set of co-regulated gene modules can be uncovered from transcriptomic variability of individuals within unperturbed populations. To robustly extract interpretable clusters from the strong noise background, we devise a novel, versatile clustering approach based on network theory. With a foundation in the generic behavior of random networks near their percolation critical point, our method is broadly applicable, beyond gene expression, to any noisy, high-dimensional data that sample variation across individuals within a population.Competing Interest StatementThe authors have declared no competing interest.View Full Text

systems biology↗

bioRxiv2018

Protein Disulfide Isomerases Control the Secretion of Wnt proteins

Appropriate Wnt morphogen secretion is required to control animal development and homeostasis. Although correct Wnt globular structure is essential for secretion, proteins that directly mediate Wnt folding and maturation are incompletely characterized. Here, we report that protein disulfide isomerase-1 (PDI-1), a protein folding catalyst and chaperone, controls secretion of the Caenorhabditis elegans Wnt ortholog EGL-20. We find that PDI-1 function is required to correctly form an anteroposterior EGL-20/Wnt gradient during embryonic development. Further, PDI-1 performs this role in EGL-20/Wnt-producing epidermal cells to cell-non-autonomously control EGL-20/Wnt-dependent neuronal migration. Using pharmacological inhibition, we further show that PDI function is required in human cells for Wnt3a secretion, revealing a conserved role for disulfide isomerases. Together, these results demonstrate a critical role for PDIs within Wnt-producing cells to control long-range developmental events that are dependent on Wnt secretion.

developmental biology↗