{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:14:06Z","timestamp":1783332846582,"version":"3.54.6"},"reference-count":122,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>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, immortalization strategies based on human telomerase reverse transcriptase (hTERT) and Simian virus 40 large T antigen (SV40) were evaluated. Electroporation-mediated transfection with SV40 successfully generated CiBCs, whereas liposome-mediated and hTERT-based approaches were unsuccessful. RNA sequencing revealed marked transcriptional changes comparing CiBCs with CpCBs, such as the upregulation of pathways related to cell cycle progression, DNA replication, and proliferation in CiBCs, together with the 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\u2013pathogen interactions, viral tolerance, and neurotropic infectious diseases relevant to emerging zoonoses.<\/jats:p>","DOI":"10.3390\/ani16132037","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:04:44Z","timestamp":1782986684000},"page":"2037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chiropteran (Hypsugo savii) Post-Natal Brain 2D-In Vitro Models: Primary Cell Isolation, Immortalization and Transcriptomic Changes"],"prefix":"10.3390","volume":"16","author":[{"given":"Antonella","family":"Molinari","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Moccia","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-4728","authenticated-orcid":false,"given":"Massimiliano","family":"Babbucci","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Peruzza","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-805X","authenticated-orcid":false,"given":"Enrico","family":"Negrisolo","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"},{"name":"Department of Agronomy, Food, Natural Resources, Animals and Environment, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7577-2107","authenticated-orcid":false,"given":"Cinzia","family":"Centelleghe","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4756-1871","authenticated-orcid":false,"given":"Sandro","family":"Mazzariol","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-0190","authenticated-orcid":false,"given":"Valentina Elena Giuditta","family":"Zappulli","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104779","DOI":"10.1016\/j.isci.2022.104779","article-title":"Molecular, Ecological, and Behavioral Drivers of the Bat-Virus Relationship","volume":"25","author":"Gonzalez","year":"2022","journal-title":"iScience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16048","DOI":"10.1038\/cddiscovery.2016.48","article-title":"Bat\u2013Man Disease Transmission: Zoonotic Pathogens from Wildlife Reservoirs to Human Populations","volume":"2","author":"Allocati","year":"2016","journal-title":"Cell Death Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.beproc.2018.06.002","article-title":"What Is Driving Range Expansion in a Common Bat? 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