Biology subjects

Dietz, C.

Publications and source records attributed to Dietz, C..

8 recordsLinked to original sources

bioRxiv2026

Large-scale cerebrospinal fluid proteomics identifies diagnostic biomarker candidates across the clinico-pathological continuum of frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD), predominantly comprised of tau and TDP-43 proteinopathies, is a common cause of early-onset dementia. Biomarkers that reliably classify FTLD subtypes are limited, thereby hindering in-vivo diagnosis and clinical trial stratification. We conducted large-scale, multi-platform cerebrospinal fluid proteomics in 566 individuals, including 274 FTLD-spectrum (48 autopsy-confirmed FTLD-TDP, 90 autopsy-confirmed FTLD-tau), 171 Alzheimers disease, and 95 controls. In neuropathological subtype contrasts, elevated matrix metalloproteinase MMP10 classified Picks disease (PiD) versus other subtypes with near-perfect accuracy across proteomic platforms. We further validated CSF MMP10 as a potential PiD diagnostic biomarker via a targeted immunoassay in an independent, autopsy-confirmed FTLD cohort. Post-synaptic proteins HOMER1 and DLG4 exhibited elevations across FTLD-TDP subtypes (A, B, and C) versus FTLD-tau. Network analysis identified RNA metabolism and pro-inflammatory signatures in FTLD-TDP, and cytoskeletal and heat shock signatures in progressive supranuclear palsy. These findings reveal candidate diagnostic biomarkers and proteomic pathways underlying FTLD clinico-pathological heterogeneity.

neuroscience↗

bioRxiv2026

Bacterial Spores as a Scalable, Modular Platform forthe Production of Amyloids for Materials

We present a proof-of-concept platform in which amyloids are displayed on the surface of engineered Bacillus subtilis spores for bioengineered materials. Amyloids possess high tensile strength, elasticity, and tunable assembly, but their use is limited by inaccessible native sources and low-yield or toxic heterologous expression. Here, spores were engineered to display the native amyloid TasA and Humboldt squid suckerins 9 and 10 as fusions to the spore coat protein CotY. Amyloid production and fibril formation were confirmed by Western blot and X-34 staining, and quantitative analysis indicated mg/L-level yields. Atomic force microscopy revealed altered stiffness and surface ultrastructure, and incorporation of amyloid-displaying spores into resin-based 3D printing modified tensile strength. These findings highlight spore-based amyloid display as a scalable, modular platform for materials applications, leveraging established industrial spore production.

bioengineering↗

bioRxiv2025

Chromatin organization controls nuclear stiffness

Cellular differentiation is driven by epigenetic modifiers and readers, including the methyl CpG binding protein 2 (MeCP2), whose level and mutations cause the neurological disorder Rett syndrome. During differentiation, most of the genome gets densely packed into heterochromatin, whose function has been simplistically viewed as gene silencing. However, gene expression changes reported in mutations leading to Rett syndrome have failed to be a predictor of disease severity. Here, we show that MeCP2 increases nuclear stiffness in a concentration dependent manner and dependent on its ability to cluster heterochromatin during differentiation. MeCP2-dependent stiffness increase could not be explained by changes in the expression of mechanobiology-related genes, but we found it is disrupted by Rett syndrome mutations and correlated with disease severity. Our results highlight the impact of chromatin organization in the mechanical properties of the cell as an alternative or complementary mechanism to changes in cytoskeleton components. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/643219v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@cb077dorg.highwire.dtl.DTLVardef@158c0c6org.highwire.dtl.DTLVardef@1d830e3org.highwire.dtl.DTLVardef@719456_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

The First Comprehensive Description of the Platelet Single Cell Transcriptome

Platelets are derived from megakaryocytes, either in peripheral or pulmonic circulation. The transcriptome of megakaryocytes has been studied, while the platelet transcriptome is thought to be a reflection of their parent cells; it has not yet been investigated. Although platelets lack nuclei, they inherit RNA from their parent megakaryocytes, while only about 10% of them are believed to contain enough RNA for meaningful analysis. This study explores the potential of single-cell RNA sequencing to analyze the platelet transcriptome, aiming to expand our understanding of platelets beyond their traditional role in coagulation. Using acridine orange staining and antibody-based sequencing, we successfully sequenced RNA from seven healthy donors. Results revealed significant heterogeneity in gene expression, with common platelet markers, such as ITGA2B and GP1B, being less abundant than expected. Interestingly, immune markers associated with lung megakaryocytes were not strongly represented in peripheral platelets. Comparison with current algorithms for cell identification suggests that platelets are often misclassified as other blood cell types, highlighting limitations of existing pipelines in platelet annotation. This misclassification may have led to misrepresentation of platelet transcriptomics in previous studies. These findings underscore the need for tailored sequencing methods to accurately profile platelets and set the foundation for further exploration of platelet biology and immune function, potentially opening avenues for therapeutic interventions in immune modulation, drug delivery, and the use of platelets as disease biomarkers in cancer and other conditions. Key PointsPlatelet single cell sequencing can be implemented with appropriate technical refinements to ensure optimal isolation without exogenous activation. In comparison to bulk sequencing techniques, single cell analysis affords the ability to exclude contaminating cells enabling examination of the authentic platelet transcriptome. This is critically important as contaminating cells contain far more RNA ultimately skewing results of transcriptomic analysis. Most platelets do not contain significant levels of commonly expected transcripts such as ITGA2B, GP1B, TREML1. In the context of recent data, our single cell transcriptomic data supports the intradividual and interindividual heterogeneity of the platelet transcriptome. The lung megakaryocyte signature is not disguisable in peripheral platelets. Further studies are needed to understand sources of RNA within platelets and the impact of the platelet microenvironment. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/618506v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@556339org.highwire.dtl.DTLVardef@1e543c4org.highwire.dtl.DTLVardef@c41cb5org.highwire.dtl.DTLVardef@138d779_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVisual abstractC_FLOATNO C_FIG

bioinformatics↗

bioRxiv2024

Nematodes Vector Bacteriophages in Compost and Soil

Bacteriophages (phages) infect bacteria to reproduce and are often lethal to their host. To maintain the infection cycle, soil phages must travel from one suitable host to the next. However, traversing the soil matrix presents a dangerous journey for phages, which need to encounter the right hosts in this spatially complex habitat, but are not capable of active motion and can adsorb to soil particles. Here, we tested the hypothesis that bacterial-feeding nematodes (roundworms) present a reliable vehicle of soil transport for phages. First, we demonstrated that the bacterivorous nematode Caenorhabditis elegans vectored the laboratory model phage T7 as well as the soil phage {Phi} Ppu-W11 on agar. Sorption assays carried out with paralyzed and non-paralyzed nematodes showed that phage transport can occur via both external cuticular attachment and ingestion, and that the presence of host bacteria is not required for phage vectoring. Finally, we designed a microcosm to test phage transfer in compost and sandy soil using C. elegans and its sister species, C. remanei, respectively. This experiment confirmed that nematodes also enable phage movement through complex spatial habitats. This novel mechanism of phage vectoring extends our understanding of virus transmission in soil, revealing new multitrophic interactions that may influence soil functioning.

ecology↗

bioRxiv2019

Induced aneuploidy disrupts MCF10A acini formation and CCND1 expression

Abnormal karyotypes, namely aneuploidy, can be detected in nearly all cancer entities at different grades. The impact of these altering mutations on epigenetic regulation, especially on promoter-enhancer interactions are not well understood. Here, we applied a 3D model of MCF10A cells in a high-content screen to measure induced aneuploidy by RNA interference of 82 mitotic genes associated with aneuploidy and breast cancer. Perturbation of ESPL1 and TOP2A expression led to increased mitotic instability and subsequent aneuploidy and polylobed nuclei. During acinus formation these polylobed cells disrupted proper acinus rotation inhibiting the development of a hollow lumen and a polarized outer cell layer. Further, gene expression profiling identified upregulated CCND1 among other breast cancer related genes. We show that acquisition of aneuploidy affects the morphogenesis of MCF10A acini and expression of cancer relevant genes. By conducting 4C chromosome capturing experiments we linked the alteration of interactions of the promoter region to CCND1 upregulation.

cancer biology↗

bioRxiv2018

Reticulate Evolutionary History of a Western Palaearctic Bat Complex Explained by Multiple mtDNA Introgressions in Secondary Contacts

AimThere is increasing evidence showing that species within various taxonomic groups have reticulate evolutionary histories with several cases of introgression events. Investigating the phylogeography of species complexes can provide insight about the introgressions, when and where these hybridizations occurred. In this study, we investigate the biogeography of a widely distributed Western Palaearctic bat species complex, namely Myotis nattereri sensu lato. This complex exhibits high genetic diversity and in its western distribution range is composed of deeply diverged genetical lineages. However, little is known about the genetic structure of the eastern populations. We also infer the conservation and taxonomical implications of the identified genetic divergences.\n\nLocationWestern Palaearctic\n\nMethodsWe analyzed 175 specimens collected from 67 locations and sequenced one mitochondrial and four nuclear DNA markers, and combined these with the available Gen-Bank sequences. We used haplotype networks, PCA, t-SNE, and Bayesian clustering algorithms to investigate the population structure and Bayesian trees to infer the phylogenetic relationship of the lineages.\n\nMain conclusionsWe identified deeply divergent genetical lineages. In some cases, nuclear and mitochondrial markers were discordant, which we interpret are caused by hybridization between lineages. We identified three such introgression events. Our findings suggest that the M. nattereri complex has a reticulate evolutionary history with multiple cases of hybridizations between some of the identified lineages. We also suggest a revision in the taxonomy of this species group, with two possible new taxa: M. hoveli and M. tschuliensis.

evolutionary biology↗

bioRxiv2018

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.

neuroscience↗