Journal
DEVELOPMENT
Volume 148, Issue 21, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.199749
Keywords
HLA; Trophoblast organoids; Trophoblast stem cells; Models; Primary cells
Categories
Funding
- Royal Society [DH160216, RGF\R1\180028]
- European Research Council under the European Union's Horizon 2020 research and innovation programme [853546]
- Centre for Trophoblast Research, University of Cambridge
- Ministerio de Ciencia e Innovacion [RYC-2019-026956, PID2020-114459RA-I00]
- Wellcome Trust Investigator Award [UNS13724]
- University of Cambridge
- European Research Council (ERC) [853546] Funding Source: European Research Council (ERC)
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Two recently developed models, trophoblast organoids and trophoblast stem cells (TSCs), are useful tools for studying human placental development. TSCs resemble cells at the base of the cell columns from where EVT derives, while organoids are similar to VCT and undergo spontaneous SCT differentiation. Understanding the HLA expression differences between these models can help in selecting the most suitable model for studying trophoblast development, function, and pathology.
Two recently developed models, trophoblast organoids and trophoblast stem cells (TSCs), are useful tools to further the understanding of human placental development. Both differentiate from villous cytotrophoblast (VCT) to either extravillous trophoblast (EVT) or syncytiotrophoblast (SCT). Here, we compare the transcriptomes and miRNA profiles of these models to identify which trophoblast they resemble in vivo. Our findings indicate that TSCs do not readily undergo SCT differentiation and closely resemble cells at the base of the cell columns from where EVT derives. In contrast, organoids are similar to VCT and undergo spontaneous SCT differentiation. A defining feature of human trophoblast is that VCT and SCT are human leukocyte antigen (HLA) null, whereas EVTexpresses HLA-C, -G and -E molecules. We find that trophoblast organoids retain these in vivo characteristics. In contrast, TSCs express classical HLA-A and HLA-B molecules, and maintain their expression after EVT differentiation, with upregulation of HLA-G. Furthermore, HLA expression in TSCs differs when grown in 3D rather than in 2D, suggesting that mechanical cues are important. Our results can be used to select the most suitable model for the study of trophoblast development, function and pathology.
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