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Feb 21, 2023, 12 tweets

Peer-reviewed paper out today! Our research created induced pluripotent stem cells from bats, revealing an unusual entanglement between bats & viruses. Provides new insights into bat biology & virus-host relationships. #batstemcells #viralbiology @CellCellPress @IcahnMountSinai

Bats have fascinated humans for centuries, but how they tolerate viruses remains a mystery. We investigate evolutionary adaptations of bats to deal with viral infections. #batimmunesystem #viralpathogens Photo: Daniel Whitby 2/

Creating bat pluripotent stem cells has been a major obstacle in bat research until now. We developed a modified Yamanaka reprogramming approach to create bat pluripotent stem cells. #batstemcells #reprogrammingfactors 3/

Bat pluripotent stem cells have a unique morphology & gene expression pattern, with tiny vesicles & expression of key pluripotency factors like Oct4. They exhibit long-term self-renewal & can differentiate into ectodermal, mesodermal, & endodermal fates & form organoids 4/

Transcriptional & epigenetic changes seen in bat stem cells suggest they’re reprogrammed both transcriptionally & epigenetically. Similarities to both naive & primed pluripotent states suggest unique & yet-to-be-characterized pluripotent default state. 5/

Comparative transcriptomics reveals bat stem cells have distinct gene expression pattern from other mammalian pluripotent stem cells & gene signature that includes unexpected categories like viral gene expression & lipid/cholesterol biosynthesis. 6/

Our study found bat pluripotent stem cells express diverse endogenized viral sequences & antigens. This suggests a particularly pro-viral environment in bat stem cells. #batstemcells #coronavirus #viralgenomics 7/

Using metagenomics, we identified previously unknown retroviral integrations & integrated DNA/RNA virus sequences in bat stem cells. Suggests sizable body of pro-viral sequences & sequence fragments inhabit the bat genome. #retrovirus #viralintegration #batgenomics 8/

Pluripotent stem cells provide a crucial tool for studying bat immunity & viral infections. By cataloging acute exogenous bat viruses & endogenous viral sequences, we can better prepare for future pandemics. #stemcells #pandemics #viralresearch 9/

Viral evolutionary processes in bat cell lines will give a better understanding of how viruses & hosts are entangled & how viruses ‘edit’ host biology. Studying bat biology can help us to better understand disease tolerance. #viralresearch #batbiology #diseasetolerance 10/

Pluripotent stem cells offer a critical research tool for studying bat biology, particularly given the challenges of establishing bat breeding colonies & primary bat cell lines. Our system will enable specific tissue & organoid studies, shedding light on bat a physiology. 11/

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