Biology subjects

Neng, L.

Publications and source records attributed to Neng, L..

3 recordsLinked to original sources

bioRxiv2026

Defects in tissue-resident macrophages lead to smaller eardrums and abnormal neurovascular networks with increased middle-ear infection

The tympanic membrane (TM), or eardrum, is essential for hearing. Macrophages, the primary innate immune cells, are densely distributed in the eardrum after birth, especially near blood vessels and nerve fibers. During postnatal development, neonatal tissue-resident macrophages (TRMs) gradually polarize, and their population declines. These dynamic changes closely parallel the maturation of neurovascular networks. What are the precursors of the early wave of TRMs? Are they critical for postnatal TM development? Using fate mapping, single-cell RNA sequencing, and macrophage depletion, this study reveals for the first time that postnatal eardrum TRMs are heterogeneous, originating mainly from embryonic myeloid lineages, with increasing input from postnatal monocyte progenitor-derived cells. Single-cell RNA sequencing identifies gene signatures vital for vascular and neuronal development. Depleting TRMs results in smaller eardrums, disrupted vascular-neuronal networks, and increased risk of middle-ear infection. This study offers new insight into how the innate immune system supports TM maturation and protects against middle-ear infection during a critical postnatal window. TeaserTissue-resident macrophages guide eardrum neurovascular maturation and help prevent middle-ear abnormalities.

immunology↗

bioRxiv2025

Monocyte-derived macrophage recruitment mediated by TRPV1 is required for eardrum wound healing

The tympanic membrane (TM), or eardrum, is a thin, sensitive tissue critical for hearing by vibrating and transmitting sound waves to the inner ear. TM perforation and development of otitis media and conductive hearing loss are commonly seen in the clinic. In this study, we demonstrate the role of TRPV1 signaling mediated macrophage recruitment and angiogenesis in TM repair. By creating a wounded TM mouse model with a perforation in the anteroinferior region of the pars tensa -- a region in humans often damaged in traumatic injury, we observed a massive accumulation of macrophages in the vicinity of the acutely wounded TM. Using 5-Ethynyl-2-deoxyuridine pause labeling and a chimeric bone marrow transplant model, we found that most of the recruited macrophages did not originate from local tissue-resident macrophages but rather from blood-circulating monocytes. Parallel to macrophage recruitment, angiogenesis was observed near the wound on day 3 after perforation and further progressed by day 7. The angiogenic process was strongly associated with the recruited macrophages, as macrophage depletion resulted in a notable reduction in angiogenesis. At the transcriptional level, we found that macrophages facilitate angiogenesis through several signaling pathways. Additionally, we identified direct intercellular communication between macrophages and endothelial cells mediated by phosphoprotein 1 signaling. Furthermore, Gene Ontology analysis of bulk RNA sequencing data from TMs revealed that the macrophage recruitment is associated with neuroinflammatory responses. Using a fluorescence reporter mouse driven by TRPV1, we discovered that the TM contains rich sensory nerve fibers expressing TRPV1. A genetic mutation in the Trpv1 gene resulted in a marked decrease in the expression of neuroinflammatory genes, such as Tac1. This decrease subsequently resulted in reduced macrophage recruitment, impaired angiogenesis, and delayed wound healing. Together, these findings highlight the crucial role of TRPV1 signaling in monocyte migration and macrophage-related angiogenesis, both of which are crucial for facilitating healing of the TM. These results also open new opportunities for clinical interventions. Targeting TRPV1 signaling could enhance TM immunity, improve blood circulation, promote the repair of damaged TM, and ultimately prevent middle ear infections.

cell biology↗

bioRxiv2022

Pericytes control vascular stability and auditory spiral ganglion neuron survival

The inner ear has a rich population of pericytes, a multi-functional mural cell essential for sensory hair cell heath and normal hearing. However, the mechanics of how pericytes contribute to the homeostasis of the auditory vascular-neuronal complex in the spiral ganglion is not yet known. In this study, using an inducible and conditional pericyte depletion mouse (PdgfrbCreERT2+/-; ROSA26iDTR+/-) model, we demonstrate, for the first time, that pericyte depletion causes loss of vascular volume and spiral ganglion neurons (SGNs) and adversely affects hearing sensitivity. Using an in vitro trans-well co-culture system, we show pericytes markedly promote neurite and vascular branch growth in neonatal SGN explants and adult SGNs. The pericyte-controlled neural growth is strongly mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A). Treatment of neonatal SGN explants or adult SGNs with pericyte-derived exosomes significantly enhances angiogenesis, SGN survival, and neurite growth, all of which were inhibited by a selective blocker of the VEGF receptor 2 (Flk1). Our study demonstrates that pericytes in the adult ear are critical for vascular stability and SGN health. Cross-talk between pericytes and SGNs via exosomes is essential for neuronal and vascular health and normal hearing.

neuroscience↗