Katherine Bianco1,2,3,4, Matthew Gormley1,2,3, Jason Farrell1,2,3, Yan Zhou1,2,3, Oliver Oliverio1,2,3, Hannah Tilden1,2,3, Michael McMaster5, Susan J Fisher6,7,8. 1. Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA. 2. Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA. 3. The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA. 4. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Stanford University School of Medicine, Stanford, CA, USA. 5. Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA. 6. Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA. sfisher@cgl.ucsf.edu. 7. Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA. sfisher@cgl.ucsf.edu. 8. The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA. sfisher@cgl.ucsf.edu.
Abstract
OBJECTIVE: Chromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy. METHODS: We profiled placental gene expression (13-22 weeks) in T13 (n = 4), T18 (n = 4) and T21 (n = 8), and in euploid pregnancies (n = 4). RESULTS: We found differentially expressed transcripts (≥2-fold) in T21 (n = 160), T18 (n = 80) and T13 (n = 125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region). CONCLUSION: The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome.
OBJECTIVE: Chromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy. METHODS: We profiled placental gene expression (13-22 weeks) in T13 (n = 4), T18 (n = 4) and T21 (n = 8), and in euploid pregnancies (n = 4). RESULTS: We found differentially expressed transcripts (≥2-fold) in T21 (n = 160), T18 (n = 80) and T13 (n = 125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region). CONCLUSION: The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome.
Authors: T Caspersson; S Farber; G E Foley; J Kudynowski; E J Modest; E Simonsson; U Wagh; L Zech Journal: Exp Cell Res Date: 1968-01 Impact factor: 3.905
Authors: Yan Zhou; Matthew J Gormley; Nathan M Hunkapiller; Mirhan Kapidzic; Yana Stolyarov; Victoria Feng; Masakazu Nishida; Penelope M Drake; Katherine Bianco; Fei Wang; Michael T McMaster; Susan J Fisher Journal: J Clin Invest Date: 2013-06-24 Impact factor: 14.808
Authors: Hiruy S Meharena; Asaf Marco; Vishnu Dileep; Elana R Lockshin; Grace Y Akatsu; James Mullahoo; L Ashley Watson; Tak Ko; Lindsey N Guerin; Fatema Abdurrob; Shruthi Rengarajan; Malvina Papanastasiou; Jacob D Jaffe; Li-Huei Tsai Journal: Cell Stem Cell Date: 2022-01-06 Impact factor: 24.633