Biology subjects

Krull, J.

Publications and source records attributed to Krull, J..

2 recordsLinked to original sources

bioRxiv2024

Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms. This iterative approach first entails single-cell spatial proteomics and rapid analysis to guide subsequent spatial transcriptomics capture on the same slide without loss in RNA signal. To enable multi-modal insights not possible with current approaches, we introduce k-bandlimited Spectral Graph Cross-Correlation (SGCC) for integrative spatial multi-omics analysis. Application of IN-DEPTH and SGCC on lymphoid tissues demonstrated precise single-cell phenotyping and cell-type specific transcriptome capture, and accurately resolved the local and global transcriptome changes associated with the cellular organization of germinal centers. We then implemented IN-DEPTH and SGCC to dissect the tumor microenvironment (TME) of Epstein-Barr Virus (EBV)-positive and EBV-negative diffuse large B-cell lymphoma (DLBCL). Our results identified a key tumor-macrophage-CD4 T-cell immunomodulatory axis differently regulated between EBV-positive and EBV-negative DLBCL, and its central role in coordinating immune dysfunction and suppression. IN-DEPTH enables scalable, resource-efficient, and comprehensive spatial multi-omics dissection of tissues to advance clinically relevant discoveries.

systems biology↗

bioRxiv2024

Polyelectrolyte mannan from diatoms reshapes sunlit ocean microbiome

Diatoms are a keystone phylum in Earths ecosystems, specializing in oxygen production and carbohydrate fixation that fuels global food webs. Diatoms host a microbiome, but how they preferentially collect bacteria with complementary traits remains unknown. Here we show that diatoms exude a C6-sulfated -1,3-mannan that serves as a selective carbon source for adapted bacteria. Its structure was resolved by NMR spectroscopy, chromatography, chemical synthesis, and enzymatic dissection. Biochemical, physiological, and structural analyses revealed that specialized Bacteroidota employ a four-enzyme pathway to metabolize this mannan. Metagenomic and transcriptomic data indicate that the mannan globally selects for bacteria carrying these enzymes and associated traits. Because the mannan provides only carbon, oxygen, sulfur, and hydrogen, bacteria must obtain other essential elements from alternative sources, reinforcing metabolic interdependence. We propose that diatoms use sulfated mannans to attract beneficial partners and exclude competitors, thereby engineering a microbiome that enhances their productivity and underpins carbon cycling. Significance statementEukaryotes host microbial partners that shape their health, yet how they selectively assemble beneficial microbes remains unclear. Using diatom microalgae as a model, we show they exude a sulfated mannan that nourishes highly adapted bacteria tracking them across the global ocean. Our findings suggest that single-celled eukaryotes can "domesticate" prokaryotes--analogous to how humans have domesticated animals--albeit on a microscopic scale. Dominating much of Earths aquatic surface, diatoms drive [~]20% of global photosynthesis. We propose that sulfated mannan contributes to this success by helping diatoms shape microbial partnerships that underpin planetary energy balance and atmospheric chemistry.

ecology↗