Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

Liuliu Yang; Yuling Han; Ting Zhou; Lauretta A. Lacko; Mohsan Saeed; Christina Tan; Ron Danziger; Jiajun Zhu; Zeping Zhao; Clare Cahir; Alice Maria Giani; Yang Li; Xue Dong; Dorota Moroziewicz; Daniel Paull; Zhengming Chen; Aaron Zhong; Scott A. Noggle; Charles M. Rice; Qibin Qi; Todd Evans; Shuibing Chen

iScience (Jul 2023)

Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

Liuliu Yang,
Yuling Han,
Ting Zhou,
Lauretta A. Lacko,
Mohsan Saeed,
Christina Tan,
Ron Danziger,
Jiajun Zhu,
Zeping Zhao,
Clare Cahir,
Alice Maria Giani,
Yang Li,
Xue Dong,
Dorota Moroziewicz,
Daniel Paull,
Zhengming Chen,
Aaron Zhong,
Scott A. Noggle,
Charles M. Rice,
Qibin Qi,
Todd Evans,
Shuibing Chen

Affiliations

Liuliu Yang: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Yuling Han: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Ting Zhou: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Lauretta A. Lacko: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Mohsan Saeed: Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA
Christina Tan: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Ron Danziger: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Jiajun Zhu: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Zeping Zhao: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Clare Cahir: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Alice Maria Giani: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Yang Li: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Xue Dong: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Dorota Moroziewicz: The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Daniel Paull: The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Zhengming Chen: Department of Population Health Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Aaron Zhong: Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Scott A. Noggle: The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA
Charles M. Rice: Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
Qibin Qi: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Todd Evans: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
Shuibing Chen: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 7
p. 107001

Abstract

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Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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