Biology subjects

Henze, D. E.

Publications and source records attributed to Henze, D. E..

3 recordsLinked to original sources

bioRxiv2026

Site-dependent transcriptomic signatures of endometriosis are conserved across hormonal states

Endometriosis, a chronic condition in which endometrial tissue grows at other sites in the body, produces lesions whose gene expression profiles vary by anatomical location and menstrual cycle stage. The extent to which these location-dependent transcriptional differences persist across hormonal states has remained unknown. Here, we compile a comprehensive single-cell RNA sequencing atlas of 672,051 cells across 112 donors from publicly available sources spanning the eutopic endometrium, menstrual effluent, ovaries, peritoneum, and ectopic endometrium from peritoneal and ovarian sites. By training machine learning classifiers on reference tissue signatures, we identify a subset of cells within ectopic lesions that retain a uterine transcriptomic identity, which we term "core" lesion cells, and which are distinguished from surrounding host tissue populations. We show that transcriptomic differences between core lesion cells at both ectopic sites are robust across all phases of the menstrual cycle and in patients receiving exogenous hormonal therapy, and validate these findings in independent datasets. Cell type- and tissue-specific gene signatures derived from these core populations are sufficient to classify disease status and lesion subtype in independent bulk tissue data across 168 patients. These findings establish that although the core lesion cells maintain elements of eutopic endometrium identity, they also contain information about the anatomical site of the lesion. This anatomic-specificity provides a potential framework for cycle-independent endometriosis diagnosis and subtyping.

bioinformatics↗

bioRxiv2025

Spatial and molecular insights into microglial roles in cerebellar aging

Aging induces region-specific functional decline across the brain. The cerebellum, critical for motor coordination and cognitive function, undergoes significant structural and functional changes with age. The molecular mechanisms driving cerebellar aging--particularly the role of cerebellar glia, including microglia--remain poorly understood. Here, we used single-nuclei RNA sequencing (snRNA-seq), microglial bulk RNA-seq, and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to characterize transcriptional changes associated with cellular aging in the mouse cerebellum. We discovered that microglia exhibited the most pronounced age-related changes of all cell types and that their transcriptional signatures pointed to enhanced neuroprotective immune activation and reduced lipid-droplet accumulation compared to hippocampal microglia. Furthermore, cerebellar microglia in aged mice, compared to young mice, were found in closer proximity to granule cells. This relationship was characterized using the newly defined neuron-associated microglia score, which captures proximity-dependent transcriptional changes and suggests a novel microglial responsiveness. These findings underscore the unique adaptations of the cerebellum during aging and its potential resilience to Alzheimers disease (AD) related pathology, providing crucial insight into region-specific mechanisms that may shape disease susceptibility.

neuroscience↗

bioRxiv2025

Simultaneous analysis of single-cell gene expression and morphology provides new insight into how microglia change with age

Cellular morphology is intimately connected with function. While the link between morphology and functional states has been studied extensively, the role of subcellular transcript localization in cellular function remains unclear. Here we use microglia, the brains resident macrophages, as a model to dissect the interaction of morphology, transcript localization, and function. Using multiplexed error-robust fluorescence in situ hybridization combined with fluorescent immunohistochemistry, we analyzed transcript distribution and morphology simultaneously in young and aged mouse brains. Our approach revealed how mRNA spatial organization varies across microglial states. We identified distinct transcript localization patterns within microglial processes and uncovered morphological heterogeneity within transcriptomically defined populations. Notably, we found a subpopulation of disease-associated microglia with a ramified morphology (displaying numerous processes), challenging the conventional assumption between morphology and microglial states. Finally, we found that aging not only alters the distribution of compartmentalized mRNAs but also reshapes their colocalization networks, shifting microglial functions from synaptic maintenance and phagocytic processes in younger brains to migration and catabolic pathways in older brains. Our findings highlight the role of subcellular transcript organization in shaping microglial morphology and function, offering new avenues for studying and modulating microglial states in health, disease, and aging.

neuroscience↗