Biology subjects

Sandmann, S.

Publications and source records attributed to Sandmann, S..

4 recordsLinked to original sources

bioRxiv2026

Spermatogonial stem cells and their differentiation roadmap throughout marmoset development

Sperm transfer genetic information from one generation to the next. These cells originate from gonocytes, which are specified during early embryonal development. To date however, there is limited information on the transcriptional gatekeepers governing the key events leading to sperm production: transition of gonocytes out of pluripotency around the time of birth, formation of the spermatogonial compartment prior to puberty, and initiation of germ cell differentiation at the time of puberty. We address this knowledge gap by employing the marmoset monkey (Callithrix jacchus) as a model for human postnatal testicular development. We analysed the transcriptional profiles of [~]48,000 neonatal, pre-pubertal, pubertal, and adult testicular cells and correlated these with histomorphometric measurements. We uncovered a transcriptional state linking gonocytes and spermatogonia characterized by CITED2 expression. Moreover, we propose NANOS2 and DPPA4 as regulators of spermatogonial plasticity from pre-puberty onwards and identify molecular gatekeepers of male germ cell differentiation.

developmental biology↗

bioRxiv2025

CD36 is a metabolic checkpoint for Th2 cell tissue residency during allergic airway inflammation

The prevalence of allergic diseases, including asthma, continues to rise in industrialized societies, yet the mechanisms sustaining pathogenic T helper 2 (Th2) responses remain incompletely understood. Here, we show that patients with allergic asthma exhibit elevated lipophilic volatile organic compounds in exhaled air and altered fatty acid-metabolism gene expression in sputum-derived Th2 cells. Using a mouse model of house dust mite-induced allergic airway inflammation, we find that the lipid transporter CD36 is dispensable for T follicular helper and germinal center B cell responses but is critical for maintaining lung-resident memory Th2 cells. CD36 regulates GATA3 and PPAR{gamma} expression in lung-resident memory Th2 cells and their interaction with type-2 conventional dendritic cells during airway inflammation. In human T cells, pharmacological inhibition of CD36 does not impair initial activation but blocks terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and establish lipid metabolism as a yet unrecognized therapeutic target in allergic asthma. SummaryAllergic asthma is marked by rising prevalence yet the drivers of persistent T helper 2 (Th2) immunity remain unclear. We show that asthma patients exhibit altered fatty acid-metabolism signatures in sputum Th2 cells and elevated lipophilic volatile organic compounds in exhaled air. In a mouse model of house dust mite-induced airway inflammation, the lipid transporter CD36 was dispensable for germinal center responses but essential for lung-resident memory Th2 cells, controlling GATA3 and PPAR{gamma} expression and promoting cDC2 interactions. Pharmacological inhibition of CD36 in human T cells preserved activation but blocked terminal Th2 differentiation. These findings identify CD36 as a metabolic checkpoint that sustains Th2 effector function and tissue residency, and nominate it as a therapeutic target in allergic asthma. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/676489v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@117da6eorg.highwire.dtl.DTLVardef@105934corg.highwire.dtl.DTLVardef@109903corg.highwire.dtl.DTLVardef@dc9345_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

PuMA: PubMed Gene-Celltype-Relation Atlas

Rapid extraction and visualization of cell-specific gene expression is important for automatic celltype annotation, e.g. in single cell analysis. There is an emerging field in which tools such as curated databases or Machine Learning methods are used to support celltype annotation. However, complementing approaches to efficiently incorporate latest knowledge of free-text articles from literature databases, such as PubMed are understudied. This work introduces the PubMed Gene/Celltype-Relation Atlas (PuMA) which provides a local, easy-to-use web-interface to facilitate automatic celltype annotation. It utilizes pretrained large language models in order to extract gene and celltype concepts from Pub-Med and links biomedical ontologies to suggest gene to celltype relations. It includes a search tool for genes and cells, additionally providing an interactive graph visualization for exploring cross-relations. Each result is fully traceable by linking the relevant PubMed articles. The software framework is freely available and enables regular article imports for incremental knowledge updates. GitLab: imigitlab.uni-muenster.de/published/PuMA

bioinformatics↗

bioRxiv2023

Genome-wide DNA methylation changes in human spermatogenesis

Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global-decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatid-specific methylome. Hypomethylated regions in spermatids were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.

genetics↗