Biology subjects

Trefzer, T.

Publications and source records attributed to Trefzer, T..

5 recordsLinked to original sources

bioRxiv2025

Latent plasticity of the human pancreas across development, health, and disease.

The pancreas plays a central role in major human diseases, yet our understanding of its cellular diversity and plasticity remains incomplete. Here, we present a single-cell multiomics atlas of the human pancreas, profiling over four million cells and nuclei from 57 donors across fetal development, adult homeostasis, and type 2 diabetes (T2D). Integrating sc/snRNA-seq, snATAC-seq, VASA-seq, spatial transcriptomics (Xenium), and multiplexed proteomics (CODEX), we resolve gene expression, chromatin accessibility, and spatial organization at high resolution. We identify transcriptionally plastic centroacinar-like cells (pCACs) in adults with fetal-like features, delineate endocrine and exocrine lineage trajectories during development, and uncover HNF1A-defined beta cell epigenetic states. In T2D, we observe shifts in beta cell subtypes and altered regulatory programs. Glucose perturbation of healthy islets reveals cell-type-specific adaptation and stress responses. This atlas provides a foundational framework to understand pancreas biology and the role of cellular plasticity in regeneration and disease.

genomics↗

bioRxiv2021

The molecular evolution of spermatogenesis across mammals

The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies and spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to be reproductively successful1,2. The rapid evolution of the testis was shown to be reflected at the molecular level based on bulk-tissue work3-8, but the molecular evolution of individual spermatogenic cell types across mammalian lineages remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from eleven species that cover the three major mammalian lineages (eutherians, marsupials, egg-laying monotremes) and birds (the evolutionary outgroup), and include seven key primates. Our analyses reveal that the rapid evolution of the testis is driven by accelerated fixation rates of gene expression changes, amino acid altering substitutions, and newly emerged genes in late spermatogenic stages - likely facilitated by reduced pleiotropic constraints, haploid selection, and a transcriptionally permissive chromatin environment. We identify temporal expression changes of individual genes across species, which may have contributed to the emergence of species-specific phenotypes, but also conserved expression programs underlying ancestral spermatogenic processes. Sex chromosome analyses show that genes predominantly expressed in spermatogonia (i.e., germ cells fueling spermatogenesis) and Sertoli cells (i.e., somatic supporting cells) independently accumulated on X chromosomes across mammals during evolution, presumably due to male-beneficial selective forces. Further work uncovered that the process of meiotic sex chromosome inactivation (MSCI) also occurs in monotremes and hence is common to the different mammalian sex chromosome systems, contrary to previous inferences9. Thus, the general mechanism of meiotic silencing of unsynapsed chromatin (MSUC), which underlies MSCI, represents an ancestral mammalian feature. Together, our study illuminates the cellular and molecular evolution of mammalian spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals.

evolutionary biology↗

bioRxiv2020

SARS-CoV-2 receptor ACE2 and TMPRSS2 are predominantly expressed in a transient secretory cell type in subsegmental bronchial branches

The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.

genomics↗

bioRxiv2019

Single nucleus RNA sequencing maps acinar cell states in a human pancreas cell atlas

Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been established, due to the local concentration of hydrolytic enzymes that can rapidly degrade cells and RNA upon resection. Here we innovated single-nucleus RNA sequencing protocols, and profiled more than 120,000 cells from adult and neonatal human donors to create the first comprehensive atlas of human pancreas cells, including epithelial and non-epithelial constituents. Adult and neonatal pancreata shared common features, including the presence of previously undetected acinar subtypes, but also showed marked differences in the composition of the endocrine, endothelial, and immune compartments. Spatial cartography, including cell proximity mapping through in situ sequencing, revealed dynamic developmental cell topographies in the endocrine and exocrine pancreas. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology, and provides a crucial reference set for future comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.

genomics↗

bioRxiv2019

Benchmarking Single-Cell RNA Sequencing Protocols for Cell Atlas Projects

Single-cell RNA sequencing (scRNA-seq) is the leading technique for charting the molecular properties of individual cells. The latest methods are scalable to thousands of cells, enabling in-depth characterization of sample composition without prior knowledge. However, there are important differences between scRNA-seq techniques, and it remains unclear which are the most suitable protocols for drawing cell atlases of tissues, organs and organisms. We have generated benchmark datasets to systematically evaluate techniques in terms of their power to comprehensively describe cell types and states. We performed a multi-center study comparing 13 commonly used single-cell and single-nucleus RNA-seq protocols using a highly heterogeneous reference sample resource. Comparative and integrative analysis at cell type and state level revealed marked differences in protocol performance, highlighting a series of key features for cell atlas projects. These should be considered when defining guidelines and standards for international consortia, such as the Human Cell Atlas project.

genomics↗