Biology subjects

Trautwein, M.

Publications and source records attributed to Trautwein, M..

3 recordsLinked to original sources

bioRxiv2025

Innate immunocompetent iNSpheroids: A hiPSC-derived 3D model to study the central nervous system captures an early CNS response to rAAV

Gene therapies using adeno-associated viruses (AAVs) for central nervous system (CNS) disorders face challenges due to host immune responses not represented in classical preclinical models. Here, we present a human-induced pluripotent stem cell (hiPSC)-derived innate immunocompetent 3D CNS model that recapitulates neuroinflammatory hallmarks, serving as a platform for preclinical gene therapy development. Utilizing various scales of stirred-tank bioreactor systems, we generated (neurospheroids) iNSpheroids composed of neurons, astrocytes, and oligodendrocytes, alongside microglial cells (iMGL) to mimic the neuro-immune axis. These systems enabled large-scale production of iNSpheroids and subsequent miniaturization for co-culture experiments and screening of inflammatory stimuli, while maintaining a highly controlled environment. The iMGL-iNSpheroids demonstrated active neuron-microglia crosstalk and exhibited distinct inflammatory responses to a series of neuroinflammatory factors. iMGL-iNSpheroids mounted a mild and transient response to rAAV9, mediated by the activation of inflammatory pathways (e.g., TNF-via NF-{kappa}B activation) in glial cell populations. This model offers a valuable tool to dissect neuroinflammatory mechanisms, accelerating gene therapy development. TeaserImmune-competent 3D human CNS model recapitulates glial responses to rAAVs, enabling reliable preclinical gene therapy screening.

bioengineering↗

bioRxiv2020

Are fleas highly modified Mecoptera? Phylogenomic resolution of Antliophora (Insecta: Holometabola)

Insect orders have been defined and stable for decades, with few notable exceptions (e.g., Blattodea and Psocoptera). One of the few remaining questions of order-level monophyly is that of Mecoptera in respect to the phylogenetic placement of Siphonaptera (fleas). We used a large set of transcriptomic nucleotide sequence data representing 56 species and more than 3,000 single-copy genes to resolve the evolutionary history of Antliophora, including fleas (Siphonaptera), scorpionflies and relatives (Mecoptera), and true flies (Diptera). We find that fleas and mecopterans together are the sister group of flies. However, our data and/or analyses are unable to distinguish whether fleas are sister to a monophyletic Mecoptera, or whether they arose from within extant mecopteran families, rendering Mecoptera paraphyletic. We did not detect parameter bias in our dataset after applying a broad range of detection methods. Counter to a previous hypothesis that placed fleas within Mecoptera as the sister group to wingless boreids (snow fleas), we found a potential sister group relationship between fleas and the enigmatic family Nannochoristidae. Although we lack conclusive evidence, it seems possible that fleas represent the most-species rich group of modern mecopterans and that their parasitic lifestyle and morphological adaptations have simply made them unrecognizable in respect to their order-level classification.

evolutionary biology↗

bioRxiv2019

Genomic characterization and curation of UCEs improves species tree reconstruction.

Ultraconserved genomic elements (UCEs), are generally treated as independent loci in phylogenetic analyses. The identification pipeline for UCE probes is agnostic to genetic identity, only selecting loci that are highly conserved, single copy, without repeats, and of a particular length. Here we characterized UCEs from 12 phylogenomic studies across the animal tree of life, from birds to marine invertebrates. We found that within vertebrate lineages, UCEs are mostly intronic and intergenic, while in invertebrates, the majority are in exons. We then curated 4 different sets of UCE markers by genomic category from 5 different studies including; birds, mammals, fish, Hymenoptera (ants, wasps and bees) and Coleoptera (beetles). Of genes captured by UCEs, we find that many are represented by 2 or more UCEs, corresponding to non-overlapping segments of a single gene. We considered these UCEs to be non-independent, merged all UCEs that belonged to a particular gene, constructed gene and species trees, and then evaluated the subsequent effect of merging co-genic UCEs on gene and species tree reconstruction. Average bootstrap support for merged UCE gene trees were significantly improved across all datasets. Increased loci length appears to drive this increase in bootstrap support. Additionally, we found that gene trees generated from merged UCEs were more accurate than those generated by unmerged and randomly merged UCEs, based on our simulation study. This modest degree of UCE characterization and curation impacts downstream analyses and demonstrates the advantages of incorporating basic genomic characterizations into phylogenomic analyses.

evolutionary biology↗