PMID- 34651188
OWN - NLM
STAT- MEDLINE
DCOM- 20211216
LR  - 20211216
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 148
IP  - 21
DP  - 2021 Nov 1
TI  - Characterization of primary models of human trophoblast.
LID - 10.1242/dev.199749 [doi]
LID - dev199749
AB  - 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 EVT expresses 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.
CI  - (c) 2021. Published by The Company of Biologists Ltd.
FAU - Sheridan, Megan A
AU  - Sheridan MA
AUID- ORCID: 0000-0002-6878-7976
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
FAU - Zhao, Xiaohui
AU  - Zhao X
AUID- ORCID: 0000-0001-9922-2815
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
AD  - Department of Physiology, Neuroscience and Development, University of Cambridge, 
      Cambridge CB2 3EG, UK.
FAU - Fernando, Ridma C
AU  - Fernando RC
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
FAU - Gardner, Lucy
AU  - Gardner L
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
FAU - Perez-Garcia, Vicente
AU  - Perez-Garcia V
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
AD  - Centro de Investigacion Principe Felipe, Eduardo Primo Yufera, Valencia 46012, 
      Spain.
FAU - Li, Qian
AU  - Li Q
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
FAU - Marsh, Steven G E
AU  - Marsh SGE
AD  - Anthony Nolan Research Institute, Royal Free Hospital, London NW3 2QG, UK.
AD  - UCL Cancer Institute, Royal Free Campus, London WC1E 6DD, UK.
FAU - Hamilton, Russell
AU  - Hamilton R
AUID- ORCID: 0000-0002-0598-3793
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
AD  - Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
FAU - Moffett, Ashley
AU  - Moffett A
AUID- ORCID: 0000-0002-8388-9073
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
FAU - Turco, Margherita Y
AU  - Turco MY
AUID- ORCID: 0000-0002-3380-7375
AD  - Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
LA  - eng
GR  - UNS13724/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211105
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (HLA Antigens)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Cell Culture Techniques
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Female
MH  - HLA Antigens/genetics/metabolism
MH  - Humans
MH  - MicroRNAs/genetics/metabolism
MH  - *Models, Biological
MH  - Organoids/cytology/growth & development/metabolism
MH  - Placentation
MH  - Pregnancy
MH  - Stem Cells/cytology/metabolism
MH  - Transcriptome
MH  - Trophoblasts/*cytology/metabolism
PMC - PMC8602945
OTO - NOTNLM
OT  - HLA
OT  - Models
OT  - Primary cells
OT  - Trophoblast organoids
OT  - Trophoblast stem cells
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2021/10/16 06:00
MHDA- 2021/12/17 06:00
PMCR- 2021/11/05
CRDT- 2021/10/15 06:43
PHST- 2021/04/26 00:00 [received]
PHST- 2021/10/01 00:00 [accepted]
PHST- 2021/10/16 06:00 [pubmed]
PHST- 2021/12/17 06:00 [medline]
PHST- 2021/10/15 06:43 [entrez]
PHST- 2021/11/05 00:00 [pmc-release]
AID - 272500 [pii]
AID - DEV199749 [pii]
AID - 10.1242/dev.199749 [doi]
PST - ppublish
SO  - Development. 2021 Nov 1;148(21):dev199749. doi: 10.1242/dev.199749. Epub 2021 Nov 
      5.