Biology subjects

Rainer, P.

Publications and source records attributed to Rainer, P..

4 recordsLinked to original sources

bioRxiv2024

Ubiquity of inverted 'gelatinous' ecosystem pyramids in the global ocean

Summary paragraphPlankton are essential in marine ecosystems. However, our knowledge of overall community structure is sparse due to inconsistent sampling across their very large organismal size range. Here we use diverse imaging methods to establish complete plankton inventories of organisms spanning five orders of magnitude in size. Plankton community size and trophic structure variation validate a long-held theoretical link between organism size-spectra and ecosystem trophic structures. We found that predator/grazer biomass and biovolume unexpectedly exceed that of primary producers at most (55%) locations, likely due to our better quantification of gelatinous organisms. Bottom- heavy ecosystems (the norm on land) appear to be rare in the ocean. Collectively, gelatinous organisms represent 30% of the total biovolume (8-9% of carbon) of marine plankton communities from tropical to polar ecosystems. Communities can be split into three extreme typologies: diatom/copepod-dominated in eutrophic blooms, rhizarian/chaetognath-dominated in oligotrophic tropical oceans, and gelatinous-dominated elsewhere. While plankton taxonomic composition changes with latitude, functional and trophic structures mostly depend on the amount of prey available for each trophic level. Given future projections of oligotrophication of marine ecosystems, our findings suggest that rhizarian and gelatinous organisms will increasingly dominate the apex position of planktonic ecosystems, leading to significant changes in the oceans carbon cycle.

ecology↗

bioRxiv2024

Dissecting reprogramming heterogeneity at single-cell resolution using scTF-seq

Reprogramming approaches often produce heterogeneous cell fates and the mechanisms behind this heterogeneity are not well-understood. To address this gap, we developed scTF-seq, a technique inducing single-cell barcoded and doxycycline-inducible TF overexpression while quantifying TF dose-dependent transcriptomic changes. Applied to mouse embryonic multipotent stromal cells (MSCs), scTF-seq produced a gain-of-function atlas for 384 murine TFs. This atlas offers a valuable resource for gene regulation and reprogramming research, identifying key TFs governing MSC lineage differentiation, cell cycle control, and their interplay. Leveraging the single-cell resolution, we dissected reprogramming heterogeneity along dose and pseudotime. We thereby revealed TF dose-dependent and stochastic cell fate branching, unveiling gene expression signatures that enhance our understanding and prediction of reprogramming efficiency. scTF-seq also allowed us to classify TFs into four sensitivity classes based on dose response and determining features. Finally, in combinatorial scTF-seq, we observed that the same TF can exhibit both synergistic and antagonistic effects on another TF depending on its dose. In summary, scTF-seq provides a powerful tool for gaining mechanistic insights into how TFs determine cell states, while offering novel perspectives for cellular engineering strategies.

cell biology↗

bioRxiv2023

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). While several mouse and human adipose SVF cellular subpopulations have now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA-seq analyses of >30 Lin-SVF samples across four human adipose depots, revealing two ubiquitous hASPC subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2- expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

cell biology↗

bioRxiv2022

Rapid differentiation of regulatory CD4+ T cells in the infarcted myocardium blunts in situ inflammation

BackgroundMyocardial infarction (MI) is a sterile inflammatory condition associated with tissue injury that results in the activation of T helper cell targeting cardiac antigens. However, the differentiation trajectories and in situ activity of heart-specific CD4+T cells activated in the MI context remain poorly understood. MethodsHerein, we combined T-cell receptor transgenic models targeting myocardial protein, single-cell transcriptomics, and functional phenotyping to elucidate how the myosin-specific CD4+ T cells (TCR-M) differentiate in the murine infarcted myocardium and ultimately influence tissue repair. Furthermore, we adoptively transferred heart-specific T-cells that were pre-differentiated in vitro towards pro-inflammatory versus regulatory phenotypic states to dissect how they differentially regulate post-myocardial infarction (MI) inflammation. ResultsFlow cytometry and single-cell transcriptomics findings reveled that transferred TCR-M cells rapidly acquired an induced regulatory phenotype (iTreg) in the infarcted myocardium and blunt local inflammation. Myocardial TCR-M cells differentiated into two main lineages enriched with cell activation and pro-fibrotic transcripts (e.g. Tgfb1) or with suppressor immune checkpoints (e.g. Pdcd1), which we also found in human myocardial tissue. These cells produced high levels of latency-associated peptide (LAP) and inhibited interleukine-17 (IL-17) responses. Notably, TCR-M cells that were pre-differentiated in vitro towards a regulatory phenotype maintained a stable in vivo FOXP3 expression and anti-inflammatory activity when adoptively transferred prior to MI induction. In contrast, TCR-M cells that were pre-differentiated in vitro towards a pro-inflammatory TH17 phenotype were partially converted towards a regulatory phenotype in the injured myocardium and blunted myocardial inflammation. ConclusionsThese findings reveal that the myocardial milieu provides a suitable environment for iTreg differentiation and reveals novels mechanisms by which the healing myocardium shapes local immunological processes.

immunology↗