2. Academic Validation
  3. Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

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

  • iScience. 2023 May 29;26(7):107001. doi: 10.1016/j.isci.2023.107001.
Liuliu Yang 1 2,  Yuling Han 1 2,  Ting Zhou 1 3,  Lauretta A Lacko 1,  Mohsan Saeed 4 5 6,  Christina Tan 1,  Ron Danziger 1,  Jiajun Zhu 1 2,  Zeping Zhao 1 2,  Clare Cahir 1,  Alice Maria Giani 1,  Yang Li 7,  Xue Dong 1,  Dorota Moroziewicz 8,  NYSCF Global Stem Cell Array® Team,  Daniel Paull 8,  Zhengming Chen 9,  Aaron Zhong 3,  Scott A Noggle 8,  Charles M Rice 4,  Qibin Qi 7,  Todd Evans 1 2,  Shuibing Chen 1 2
Affiliations

Affiliations

  • 1 Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • 2 Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • 3 Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
  • 4 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 5 Department of Biochemistry & Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
  • 6 National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.
  • 7 Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
  • 8 The New York Stem Cell Foundation Research Institute, 619 West 54th Street, 3Road Floor, New York, NY 10019, USA.
  • 9 Department of Population Health Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
PMID: 37534130 DOI: 10.1016/j.isci.2023.107001
Abstract

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.

Keywords

Stem cells research; Virology.

Figures
Products