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Identification of cell type specific ACE2 modifiers by CRISPR screening.
Sherman, Emily J; Mirabelli, Carmen; Tang, Vi T; Khan, Taslima G; Leix, Kyle; Kennedy, Andrew A; Graham, Sarah E; Willer, Cristen J; Tai, Andrew W; Sexton, Jonathan Z; Wobus, Christiane E; Emmer, Brian T.
Afiliación
  • Sherman EJ; Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Mirabelli C; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Tang VT; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Khan TG; Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Leix K; Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Kennedy AA; Chemical Biology Program, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Graham SE; Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Willer CJ; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Tai AW; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Sexton JZ; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Wobus CE; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Emmer BT; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS Pathog ; 18(3): e1010377, 2022 03.
Article en En | MEDLINE | ID: mdl-35231079
SARS-CoV-2 infection is initiated by binding of the viral spike protein to its receptor, ACE2, on the surface of host cells. ACE2 expression is heterogeneous both in vivo and in immortalized cell lines, but the molecular pathways that govern ACE2 expression remain unclear. We now report high-throughput CRISPR screens for functional modifiers of ACE2 surface abundance. In liver-derived HuH7 cells, we identified 35 genes whose disruption was associated with a change in the surface abundance of ACE2. Enriched among these ACE2 regulators were established transcription factors, epigenetic regulators, and functional networks. We further characterized individual HuH7 cell lines with disruption of SMAD4, EP300, PIAS1, or BAMBI and found these genes to regulate ACE2 at the mRNA level and to influence cellular susceptibility to SARS-CoV-2 infection. Orthogonal screening of lung-derived Calu-3 cells revealed a distinct set of ACE2 modifiers comprised of ACE2, KDM6A, MOGS, GPAA1, and UGP2. Collectively, our findings clarify the host factors involved in SARS-CoV-2 entry, highlight the cell type specificity of ACE2 regulatory networks, and suggest potential targets for therapeutic development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos