title: What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast.
abstract: Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP)-treated human ESC and 2102Ep, an embryonal carcinoma cell line. Both cell types only show some, but not all, of the four trophoblast criteria. Thus, BMP-treated human ESC have not fully differentiated to trophoblast. Our study identifies a robust panel, including both protein and non-protein-coding markers that, in combination, can be used to reliably define cells as characteristic of early trophoblast.
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada. Electronic address: qecl2@cam.ac.uk.
authors: Cheryl Q E
authors: CQ
authors: Lee
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors: Lucy
authors: L
authors: Gardner
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors: Margherita
authors: M
authors: Turco
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Nancy
authors: N
authors: Zhao
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Matthew J
authors: MJ
authors: Murray
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors: Nicholas
authors: N
authors: Coleman
authors: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5G 0A4, Canada.
authors: Janet
authors: J
authors: Rossant
authors: Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors: Myriam
authors: M
authors: Hemberger
authors: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: am485@cam.ac.uk.
authors: Ashley
authors: A
authors: Moffett
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D009626:Terminology as Topic; D014157:Transcription Factors; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; D015395:Histocompatibility Antigens Class I; D035683:MicroRNAs; C115711:PD 173074; D050783:Proto-Oncogene Proteins c-ets; D011743:Pyrimidines; D014157:Transcription Factors; D005346:Fibroblast Growth Factors