Biology subjects

Luca, E.

Publications and source records attributed to Luca, E..

4 recordsLinked to original sources

bioRxiv2026

A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells

Mechanosensitive hair cells vary widely in morphology and regenerative capacity across vertebrate organs and species. To investigate their underlying transcriptomic diversity, we integrated human, mouse, chicken, and zebrafish single-cell and single-nucleus RNA sequencing datasets and assembled a cross-species atlas of hair cells spanning organs, developmental stages, and species. Analysis of 29 hair cell populations, encompassing the major cochlear, vestibular, and lateral-line hair cell types, identified approximately 5,000 genes enriched in at least one hair cell population compared to supporting cells from the same organs. Unsupervised clustering of these hair cell-enriched (HCE) genes defined species-, organ-, and hair cell state-associated cohorts as well as broadly conserved hair cell-enriched programs. Using an AUC-based scoring framework, we further defined 884 pan hair cell-enriched (pan-HCE) genes with elevated expression in most developing and/or mature hair cell populations, including genes implicated in deafness, mechanotransduction, and synaptic transmission, along with genes not previously linked to hair cell function. Independent analysis of developing hair cells using the same metrics stratified pan-HCE genes based on when they are first enriched and identified an additional 97 genes that are transiently enriched. We used the pan- and developing HCE gene sets to assess transcriptional similarity between baseline hair cell states and hair cells produced during avian hair cell regeneration and in mouse cochlear organoids, as well as hair cell-like populations produced by fibroblast reprogramming. HCE gene sets with different developmental dynamics identified young vs. more mature hair cells when projected onto independent single-cell RNA sequencing datasets from developing zebrafish, mouse, and human. We provide a web-based resource of all HCE metrics and expression profiles, enabling future exploration of vertebrate hair cell gene expression across organs, species, and experimental contexts.

neuroscience↗

bioRxiv2026

Spatiotemporal cellular landscape of the human utricle sensory epithelium

Vestibular dysfunction affects individuals of all ages and becomes increasingly common with age. Despite the essential role of the utricle in balance, its molecular states and tissue architecture in humans remain poorly defined. Here, we integrated paired single-nucleus transcriptomic and epigenomic profiling with imaging-based spatial transcriptomics to characterize the human fetal utricle and its spatiotemporal patterning. We resolved transcriptionally heterogeneous, spatially segregated populations of sensory and nonsensory epithelial cells and reconstructed sensory cell differentiation across three gestational ages, showing that these cells acquire region-specific transcriptional signatures before final subtype specification. We further uncover a progressive decline in nonsensory cell proliferation accompanied by chromatin remodelling, as well as transitional epithelial populations with distinct spatial and regulatory programs. Together, these data define the molecular and spatial dynamics of the human fetal utricle and reveal cell states and regulatory pathways that provide a foundation for studying vestibular disorders and regeneration. HIGHLIGHTSO_LISpatial identity of utricular sensory hair cells precedes full subtype specification C_LIO_LIDistinct transcriptional regulators control hair cell fate and regional patterning C_LIO_LISupporting cells remodel chromatin as their proliferative capacity declines C_LIO_LITransitional epithelial cells adopt ordered states along the utricular border C_LIO_LISensory and nonsensory cells show divergent regulatory and signalling programs C_LI

cell biology↗

bioRxiv2025

Trophic and temporal dynamics of macrophage biology in human inner ear organogenesis

Recent single-cell transcriptomic approaches are uncovering the breadth and depth of cell diversity within the mammalian inner ear. Macrophages, detected from gestational week 7 in the human inner ear, persist into adulthood, and yet remain poorly understood in terms of their origin and function. Using self-generated and public scRNA-seq data, we identify seven distinct macrophage subtypes spanning fetal weeks 7.5 to 16.4 and adulthood. Each macrophage subtype is linked to specific developmental stages and displays a unique gene expression profile. These findings corroborate earlier histological evidence of resident and non-resident macrophages in both the developing and adult human cochlea. We also show that the human inner ear is seeded by macrophages from both embryonic and more definitive sources, corroborating studies in mouse. By analyzing ligand-receptor interactions, we highlight potential macrophage contributions to inner ear organogenesis. This research provides new insights into the diverse roles of human inner ear macrophages.

bioinformatics↗

bioRxiv2022

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

cancer biology↗