Characterization of primary models of human trophoblast.
Por:
Sheridan MA, Zhao X, Fernando RC, Gardner L, Perez-Garcia V, Li Q, Marsh SGE, Hamilton R, Moffett A and Turco MY
Publicada:
1 nov 2021
Ahead of Print:
15 oct 2021
Resumen:
Although understanding of human placental development is still limited, two models, trophoblast organoids and trophoblast stem cells (TSC) provide new useful tools to study this. Both differentiate from villous cytotrophoblast (VCT) to either extravillous trophoblast (EVT) or syncytiotrophoblast (SCT). Here, we compare transcriptomes and miRNA profiles of these models to identify which trophoblast they resemble in vivo. Our findings indicate that TSC do not readily undergo SCT differentiation and closely resemble cells at the base of the cell columns from where EVT are derived. In contrast, organoids are similar to VCT and undergo spontaneous SCT differentiation. A defining feature of human trophoblast is that VCT and SCT are HLA null whilst EVT express HLA-C, -G, -E molecules. We find that trophoblast organoids retain these in vivo characteristics. In contrast, TSC do express classical HLA-A and HLA-B molecules and still maintain their expression after EVT differentiation with upregulation of HLA-G. Furthermore, HLA expression in TSC differs when grown in 3D rather than 2D suggesting mechanical cues are important. Our results will allow choice of the most suitable model to study trophoblast development, function and pathology.
Filiaciones:
Sheridan MA:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Zhao X:
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Department of Physiology, Neuroscience and Development, University of Cambridge, Cambridge, UK
Fernando RC:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Gardner L:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, Valencia, Spain
Li Q:
Department of Pathology, University of Cambridge, Cambridge, UK
Department of Genetics, University of Cambridge, Cambridge, UK
Marsh SGE:
Anthony Nolan Research Institute, Royal Free Hospital, London, UK
UCL Cancer Institute, Royal Free Campus, London, UK
Hamilton R:
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Department of Genetics, University of Cambridge, Cambridge, UK
Moffett A:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Turco MY:
Department of Pathology, University of Cambridge, Cambridge, UK
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
Green Published, hybrid
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