Biology subjects

Waldherr, M.

Publications and source records attributed to Waldherr, M..

4 recordsLinked to original sources

bioRxiv2024

HDAC1 controls the generation and maintenance of effector-like CD8+ T cells during chronic viral infection

CD8+ T cell exhaustion is a complex process that involves the differentiation of persistently activated CD8+ T cells into functionally distinct cell subsets. Here, we investigated the role of the key epigenetic regulator histone deacetylase 1 (HDAC1) in the differentiation of exhausted T (Tex) cells during chronic viral infection. We uncovered that HDAC1 controls the generation and maintenance of effector-like CX3CR1+ Tex cells in a CD8+ T cell-intrinsic manner. Deletion of HDAC1 led to expansion of an alternative Tex cell subset characterized by high expression of T cell exhaustion markers, and this was accompanied by elevated viremia. HDAC1 knockout altered the chromatin landscape in progenitor Tex cells, abrogated the expression of effector-like signature genes and interfered with cell fate specification toward the CX3CR1+ Tex cell subset. We conclude that HDAC1 is functionally required for controlling viral load during chronic infection by ensuring adequate CX3CR1+ Tex cell subset differentiation. HighlightsO_LIHDAC1 promotes the generation of CX3CR1+ effector-like Tex cell subsets in chronic viral infection in a CD8+ T cell-intrinsic manner. C_LIO_LIDeletion of HDAC1 leads to an increase of a cell subset enriched in exhaustion markers and is accompanied with elevated viremia. C_LIO_LIHDAC1 is required for the maintenance of the CX3CR1+ Tex cell pool. C_LIO_LIHDAC1 deletion alters the chromatin landscape at effector-like signature gene loci in progenitor Tex cells. C_LI

immunology↗

bioRxiv2023

Single-cell profiling uncovers regulatory programs of pathogenic Th2 cells in allergic asthma

Lung pathogenic T helper type 2 (pTh2) cells are important drivers of allergic asthma, but fundamental questions remain regarding their regulation and heterogeneity. The differentiation and effector functions of immune cells are tightly regulated by epigenetic processes. Histone deacetylase 1 (HDAC1) is an important epigenetic regulator of T cells, however, its role in pTh2 cells is yet to be determined. Here we investigate immune regulation in allergic asthma by single-cell RNA sequencing (scRNA-seq) in mice challenged with house dust mite, in the presence and absence of HDAC1 function. Our analyses reveal two distinct subsets of lung pTh2 cells: pathogenic effector Th2 (peTh2) and pathogenic Th2 tissue-resident memory (Th2 Trm) cells. Both pTh2 cell subsets are highly proinflammatory and exhibit distinct transcriptional and phenotypic signatures as compared with other lung Th subsets. Based on our scRNA-seq analysis, we identify conditions to generate pTh2 cells in vitro and confirm that these in vitro generated pTh2 cells have a similar transcriptional profile as lung peTh2 cells. Using our new in vitro model, we demonstrate that the p38 mitogen-activated protein kinase pathway is critical for interleukin-5 (IL-5) and IL-13 expression in pTh2 cells. Our data further underline the importance of HDAC1 in limiting the pathogenicity of lung and in vitro pTh2 cells and in the formation of lung Th2 Trm cells. In summary, we have generated novel insights into pTh2 cell biology and established a new in vitro model for investigating pTh2 cells that will be useful for discovering molecular mechanisms involved in pTh2-mediated allergic asthma.

immunology↗

bioRxiv2021

Analyses of cephalic and non-cephalic sensory cell types provide insight into joint photo- and mechanoreceptor evolution

Rhabdomeric Opsins (r-Opsins) are light-sensors in cephalic eye photoreceptors, but also function in additional sensory organs. This has prompted questions on the evolutionary relationship of these cell types, and if ancient r-Opsins cells were non-photosensory. Our profiling of cephalic and non-cephalic r-opsin1-expressing cells of the marine bristleworm Platynereis dumerilii reveals shared and distinct features. Non-cephalic cells possess a full set of phototransduction components, but also a mechanosensory signature. We determine that Pdu-r-Opsin1 is a Gq-coupled blue-light receptor. Profiling of cells from r-opsin1 mutants versus wild-types, and a comparison under different light conditions reveals that in the non-cephalic cells, light - mediated by r-Opsin1 - adjusts the expression level of a calcium transporter relevant for auditory mechanosensation in vertebrates. We establish a deep learning-based quantitative behavioral analysis for animal trunk movements, and identify a light-and r-Opsin-1-dependent fine-tuning of the worms undulatory movements in headless trunks, which are known to require mechanosensory feedback. Our results suggest an evolutionary concept in which r-Opsins act as ancient, light-dependent modulators of mechanosensation, and suggest that light-independent mechanosensory roles of r-Opsins likely evolved secondarily.

developmental biology↗

bioRxiv2020

European Primary Forest Database (EPFD) v2.0

Primary forests are scarce in Europe and continue to disappear at an alarming rate. Despite these losses, we know little about where such forests still occur. Here, we present an updated geodatabase and map of Europes known primary forests. Our geodatabase harmonizes 48 different datasets of primary forests, and contains 18,411 individual patches (41.1 Mha) spread across 33 countries. When available, we provide information on each patch (name, location, naturalness, extent and dominant tree species) and the surrounding landscape (biogeographical regions, protection status, potential natural vegetation, current forest extent). To assess the robustness of our geodatabase, we checked each patch for forest disturbance events using Landsat satellite-image time series (1985-2018). We estimate that 94% of the patches in our database did not experience significant disturbances that would alter their primary forest status in the last 30 year. Our database is the most comprehensive dataset on primary forests in Europe, and will be useful for biogeographic and ecological studies, and conservation planning to safeguard these unique forests.

ecology↗