Work

Chiropteran (Hypsugo savii) Post-Natal Brain 2D-In Vitro Models: Primary Cell Isolation, Immortalization and Transcriptomic Changes

Year: 2026

Type: article

Abstract: Bats are important reservoirs of zoonotic pathogens and valuable models for studying antiviral tolerance and neuroinflammation within a One Health framework. However, chiropteran neural 2D-in vitro models remain limited. Here, we established and characterized the first chiropteran primary (CpBCs) and immortalized (CiBCs) cell lines from Hypsugo savii species. To overcome the limited lifespan of CpBCs, immor-talization strategies based on human telomerase reverse transcriptase (TERT) and Simian virus 40 (SV40) large T antigen were evaluated. Electroporation-mediated transfection with SV40 successfully generated CiBCs, whereas liposome-mediated and TERT-based approaches were unsuccessful. RNA sequencing revealed marked tran-scriptional changes comparing CiBCs with CpCBs, such as upregulation of pathways related to cell cycle progression, DNA replication, and proliferation in CiBCs, together with downregulation of apoptosis, inflammatory signaling, and immune-related pathways. Immortalized cells also exhibited enrichment of neural stem cell–like and cancer-associated signatures, suggesting partial dedifferentiation induced by SV40-mediated immortalization. Overall, this study provides a novel chiropteran brain-derived 2D-in vitro platform for investigating bat neurobiology, host–pathogen interactions, viral tolerance, and neurotropic infectious diseases relevant to emerging zoonoses.

Source: Animals

DOI: 10.3390/ani16132037