Biology subjects

Senn, P.

Publications and source records attributed to Senn, P..

3 recordsLinked to original sources

bioRxiv2026

LGR5 and SOX2 expressing progenitor cells in the adult and aged human and mouse inner ear have the potential to produce Myosin 7A positive cells in vitro

Hearing loss and deafness as a result of hair cell loss cannot be restored due to the incapacity of spontaneous regeneration of these cells. Compounds that manipulate key signaling pathways can potentially regenerate cochlear hair cells. In order to test different compounds that promote hair cell regeneration in vitro models can be used. Three-dimensional cultures have allowed the expansion and experimentation of human and mouse inner ear organoids. This is mainly performed in the embryonic or the early postnatal developmental stage. However, since the majority of patients with hearing loss are adult, it is crucial to understand the adult inner ear regenerative capacity. Here, we evaluated progenitor cell markers in the adult human and mouse inner ear and the generation, expansion and differentiation of cochlear organoids derived from the adult human and mouse inner ear. Cochlear and vestibular sensory epithelium from adult humans; and from adult and aged mice express the progenitor markers SOX2 and LGR5; and can generate organoids in vitro. By optimizing the culture conditions, organoids derived from the cochlea and vestibular organ from adult human and adult and aged mouse differentiated to Myosin 7A positive cells. This indicates that the adult inner ear has regenerative capacity. These findings are encouraging for future regenerative therapies to cure hair cell-related hearing loss and deafness.

neuroscience↗

bioRxiv2026

Whole human organ clearing and multimodal mapping

Human anatomy has traditionally been studied using low-resolution approaches such as cadaveric dissection and conventional medical imaging, limiting our understanding of macroscopic structures. Tissue clearing has emerged as a transformative approach, enabling three-dimensional mapping of organs at microscopic resolution, and offering the opportunity to interrogate anatomy across scales. However, its application to human organs remains challenging due to their size, density and optical properties. Here, we establish multiorgan CleLight (mCleLight) as a generalizable method for clearing, labeling and imaging whole human tissues. mCleLight is broadly applicable across major organ systems and enables the analysis of particularly challenging specimens, including highly heterogeneous samples, dense bones, pigmented tissues and decades-old formalin-fixed archival material. We demonstrate that controlled photoclearing is critical across human tissues both for efficient clearing and for quenching endogenous fluorescence, thereby substantially improving imaging depth as compared to previous methods. mCleLight allows specific labeling and quantitative analysis of complex extended structures such as collagen fibers, vasculature, and innervation, while preserving anatomical relationships, which cannot be easily done with classical histology. We integrated mCleLight into a pipeline with clinical imaging to achieve a comprehensive, multiscale understanding of organ architecture. We demonstrate the voxel-by-voxel alignment between MRI and microscopy datasets, merging cellular-scale detail and protein- specific labeling with macroscopic medical imaging. By bridging the gap between imaging scales and modalities, mCleLight provides a versatile method for integrated three- dimensional histological mapping and macroscopic anatomy of human organs in health and disease.

cell biology↗

bioRxiv2025

Introducing a translationally relevant mouse model of radiosurgery-induced unilateral hearing loss

BackgroundStereotactic radiosurgery (SRS) is widely used to treat vestibular schwannomas but may cause irreversible hearing loss due to cochlear toxicity. The underlying mechanisms are not fully understood, and no effective otoprotective therapies exist. We aimed to establish a mouse model that replicates the clinical pattern of radiation-induced hearing loss. MethodsC57BL/6J mice (n=31) received 8 Gy (n=3), 16 Gy (n=5), 24 Gy (n=8), or 32 Gy (n=15) using the Leksell Gamma Knife ICON system. Targeting was based on the built-in cone-beam CT, co-registered with MRI and CT-based mouse atlases, to guide unilateral cochlea targeting. A single isocenter was placed lateral to the right cochlea, with the 80% isodose line traversing its medial edge. Auditory brainstem response (ABR) was measured at baseline and at 1 and 4 weeks post-SRS. A 32 Gy subgroup (n=7) was evaluated at 16 weeks. Histological analysis of cochleae was performed at 4 weeks in all groups and at 16 weeks in the long-term 32 Gy group. ResultsSRS was well tolerated, and the contralateral cochlea received a very low radiation dose. No ABR shifts were observed at 8 or 16 Gy, with only minimal histological changes. At 32 Gy, ABR threshold shifts at 22.6 and 32 kHz were evident by week 1 and worsened by week 4. Similar but milder effects occurred at 24 Gy. In the 32 Gy long-term subgroup, hearing loss progressed across all frequencies, most severely at high frequencies, alongside a sustained wave I amplitude decline. At 32 Gy, outer hair cells were reduced by 14% and 44% at 32 and 45.2 kHz, respectively, at 4 weeks, and by 38% and 80% at 16 weeks. Ribbon synapses were mildly reduced at 4 weeks and more markedly at 16 weeks in corresponding high-frequency regions. Spiral ganglion neuron density was mildly reduced at the basal and middle turns. All reported changes were statistically significant when compared to the contralateral ear. ConclusionsThis new model reproduces key features of SRS-induced cochlear toxicity, including unilateral, dose-dependent, and progressive hearing loss. It thus provides a valuable platform for investigating mechanisms and testing otoprotective strategies.

neuroscience↗