Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Marion Déjosez; Arturo Marin; Graham M Hughes; Ariadna E Morales; Carlos Godoy-Parejo; Jonathan L Gray; Yiren Qin; Arun A Singh; Hui Xu; Javier Juste; Carlos Ibáñez; Kris M White; Romel Rosales; Nancy J Francoeur; Robert P Sebra; Dominic Alcock; Thomas L Volkert; Sébastien J Puechmaille; Andrzej Pastusiak; Simon D W Frost; Michael Hiller; Richard A Young; Emma C Teeling; Adolfo García-Sastre; Thomas P Zwaka

doi:10.1016/j.cell.2023.01.011

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Cell. 2023 Mar 2;186(5):957-974.e28. doi: 10.1016/j.cell.2023.01.011. Epub 2023 Feb 21.

Authors

Marion Déjosez¹, Arturo Marin², Graham M Hughes³, Ariadna E Morales⁴, Carlos Godoy-Parejo⁵, Jonathan L Gray⁵, Yiren Qin⁵, Arun A Singh⁵, Hui Xu⁵, Javier Juste⁶, Carlos Ibáñez⁷, Kris M White², Romel Rosales², Nancy J Francoeur⁸, Robert P Sebra⁹, Dominic Alcock³, Thomas L Volkert¹⁰, Sébastien J Puechmaille¹¹, Andrzej Pastusiak¹², Simon D W Frost¹³, Michael Hiller¹⁴, Richard A Young¹⁵, Emma C Teeling¹⁶, Adolfo García-Sastre¹⁷, Thomas P Zwaka¹⁸

Affiliations

¹ Huffington Center for Cell-Based Research in Parkinson's disease, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Department of Cell, Developmental, and Regenerative Biology, and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Paratus Sciences, 430 East 29th Street, Suite 600, New York, NY 10016, USA.
² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
³ School of Biology and Environmental Science, University College Dublin, Ireland.
⁴ Senckenberg Research Institute, Senckenberganlage 25, 60325 Frankfurt, Germany; Faculty of Biosciences, Goethe University, Max-von-Laue-Str, 60438 Frankfurt, Germany.
⁵ Huffington Center for Cell-Based Research in Parkinson's disease, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Department of Cell, Developmental, and Regenerative Biology, and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
⁶ Estación biológica de doñana (CSIC), Avda. Américo Vespucio 26, Seville 41092, Spain; CIBER Epidemiology and Public Health, CIBERESP, Madrid, Spain.
⁷ Estación biológica de doñana (CSIC), Avda. Américo Vespucio 26, Seville 41092, Spain.
⁸ Pacific Biosciences, Menlo Park, CA, USA.
⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Genomics, New York, NY, USA.
¹⁰ Paratus Sciences, 430 East 29th Street, Suite 600, New York, NY 10016, USA.
¹¹ ISEM, University of Montpellier, Montpellier, France.
¹² Microsoft Premonition, Microsoft Building 99, 14820 NE 36th Street, Redmond, WA 98052, USA.
¹³ Microsoft Premonition, Microsoft Building 99, 14820 NE 36th Street, Redmond, WA 98052, USA; Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
¹⁴ LOEWE Centre for Translational Biodiversity Genomics, Senckenberganlage 25, 60325 Frankfurt, Germany; Senckenberg Research Institute, Senckenberganlage 25, 60325 Frankfurt, Germany; Faculty of Biosciences, Goethe University, Max-von-Laue-Str, 60438 Frankfurt, Germany.
¹⁵ Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
¹⁶ School of Biology and Environmental Science, University College Dublin, Ireland. Electronic address: emma.teeling@ucd.ie.
¹⁷ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine and the Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: adolfo.garcia-sastre@mssm.edu.
¹⁸ Huffington Center for Cell-Based Research in Parkinson's disease, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Department of Cell, Developmental, and Regenerative Biology, and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Paratus Sciences, 430 East 29th Street, Suite 600, New York, NY 10016, USA. Electronic address: thomas.zwaka@mssm.edu.

Abstract

Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However, there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) and the greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences, particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.

Keywords: bats; cancer; coronaviruses; differentiation; endogenized viruses; epigenetics; evolution; host-pathogen-interactions; induced pluripotent stem cells; inflammation; virus response.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Chiroptera*
Phylogeny
Pluripotent Stem Cells*
Transcriptome
Virus Diseases*
Viruses* / genetics

Abstract

Publication types

MeSH terms

Grants and funding