ARID3A is required for mammalian placenta development
Open accessAbstract
Previous studies in the mouse indicated that ARID3A plays a critical role in the first cell fate decision required for generation of trophectoderm (TE). Here, we demonstrate that ARID3A is widely expressed during mouse and human placentation and essential for early embryonic viability. ARID3A localizes to trophoblast giant cells and other trophoblast-derived cell subtypes in the junctional and labyrinth zones of the placenta. Conventional Arid3a knockout embryos suffer restricted intrauterine growth with severe defects in placental structural organization. Arid3a null placentas show aberrant expression of subtype-specific markers as well as significant alteration in cytokines, chemokines and inflammatory response-related genes, including previously established markers of human placentation disorders. BMP4-mediated induction of trophoblast stem (TS)-like cells from human induced pluripotent stem cells results in ARID3A up-regulation and cytoplasmic to nuclear translocation. Overexpression of ARID3A in BMP4-mediated TS-like cells up-regulates TE markers, whereas pluripotency markers are down-regulated. Our results reveal an essential, conserved function for ARID3A in mammalian placental development through regulation of both intrinsic and extrinsic developmental programs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Five candidate TFs (ARID3A, C/EBPα, FOXA3, MYBL2, SOX13) are identified by overlapping TF enrichment and co-expression with GPC3.
“By overlapping these lists, we identified five candidate TFs: ARID3A, C/EBPα, FOXA3, MYBL2, and SOX13, most of which are overexpressed in HCC and are implicated in hepatocarcinogenesis (Supplementary Fig. 6b, c)69–73.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [71]
The five-TF list is presented in the citing sentence as the citing authors’ own identification, not as a finding attributed to this source. The source’s Results sections 6–7 examine ARID3A in trophoblast and placental development; searches for GPC3, the other listed TFs, and HCC found no passage addressing the citation-linked claim about overexpression or hepatocarcinogenesis. No page numbers were available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hemberger, M., Udayashankar, R., Tesar, P., Moore, H., & Burton, G. J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq128 · Cited by 181 · see citing works
Flagged first, then by citations
Research works printed but not linked: 38
- Ananth CV Keyes KM Wapner RJ 2013 Pre-eclampsia rates in the United States, 1980–2010: age-period-cohort analysis Bmj 347 f6564 24201165 PMC3898425
- Bainbridge SA Minhas A Whiteley KJ Qu D Sled JG Kingdom JC Adamson SL 2012 Effects of reduced Gcm1 expression on trophoblast morphology, fetoplacental vascularity, and pregnancy outcomes in mice Hypertension 59 732 739 22275534
- Bernardo AS Faial T Gardner L Niakan KK Ortmann D Senner CE Callery EM Trotter MW Hemberger M Smith JC 2011 BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages Cell stem cell 9 144 155 21816365 PMC3567433
- Bilban M Haslinger P Prast J Klinglmuller F Woelfel T Haider S Sachs A Otterbein LE Desoye G Hiden U 2009 Identification of novel trophoblast invasion-related genes: heme oxygenase-1 controls motility via peroxisome proliferator-activated receptor gamma Endocrinology 150 1000 1013 18845641 PMC3064984
- Chen CP Chen CY Yang YC Su TH Chen H 2004 Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia Placenta 25 413 421 15081636
- Dietrich JE Hiiragi T 2007 Stochastic patterning in the mouse pre-implantation embryo Development 134 4219 4231 17978007
- Ezashi T Telugu BP Roberts RM 2012 Model systems for studying trophoblast differentiation from human pluripotent stem cells Cell and tissue research 349 809 824 22427062 PMC3429771
- Founds SA Terhorst LA Conrad KP Hogge WA Jeyabalan A Conley YP 2011 Gene expression in first trimester preeclampsia placenta Biological research for nursing 13 134 139 21044967 PMC3598011
- Fournier T Therond P Handschuh K Tsatsaris V Evain-Brion D 2008 PPARgamma and early human placental development Current medicinal chemistry 15 3011 3024 19075649
- Guillemot F Nagy A Auerbach A Rossant J Joyner AL 1994 Essential role of Mash-2 in extraembryonic development Nature 371 333 336 8090202
- Hay DC Sutherland L Clark J Burdon T 2004 Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells Stem cells 22 225 235 14990861
- Kidder BL Palmer S 2010 Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance Genome research 20 458 472 20176728 PMC2847749
- Kim PG Canver MC Rhee C Ross SJ Harriss JV Tu HC Orkin SH Tucker HO Daley GQ 2016 Interferon-alpha signaling promotes embryonic HSC maturation Blood PMC4946201 27095787
- Levine RJ Lam C Qian C Yu KF Maynard SE Sachs BP Sibai BM Epstein FH Romero R Thadhani R 2006 Soluble endoglin and other circulating antiangiogenic factors in preeclampsia The New England journal of medicine 355 992 1005 16957146
- Li Y Moretto-Zita M Soncin F Wakeland A Wolfe L Leon-Garcia S Pandian R Pizzo D Cui L Nazor K 2013 BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a DeltaNp63+ cytotrophoblast stem cell state Development 140 3965 3976 24004950 PMC3775414
- Li Y Parast MM 2014 BMP4 regulation of human trophoblast development The International journal of developmental biology 58 239 246 25023690 PMC5373803
- Martinez-Fierro ML Reyes-Oliva EA Cabral-Pacheco GA Garza-Veloz I Aceves-Medina MC Luevano M Barbosa-Cisneros OY Galvan-Valencia M Yahuaca-Mendoza P Delgado-Enciso I 2016 MYC-induced nuclear antigen (MINA) and preeclampsia Hypertension in pregnancy 1 13 26910584
- Mikheev AM Nabekura T Kaddoumi A Bammler TK Govindarajan R Hebert MF Unadkat JD 2008 Profiling gene expression in human placentae of different gestational ages: an OPRU Network and UW SCOR Study Reproductive sciences 15 866 877 19050320 PMC2702165
- Molineris I Grassi E Ala U Di Cunto F Provero P 2011 Evolution of promoter affinity for transcription factors in the human lineage Molecular biology and evolution 28 2173 2183 21335606
- Niakan KK Eggan K 2013 Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse Developmental biology 375 54 64 23261930
- Niwa H 2007 How is pluripotency determined and maintained? Development 134 635 646 17215298
- Perez-Sepulveda A Torres MJ Khoury M Illanes SE 2014 Innate immune system and preeclampsia Frontiers in immunology 5 244 24904591 PMC4033071
- Rhee C Lee BK Beck S Anjum A Cook KR Popowski M Tucker HO Kim J 2014 Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation Genes & development 28 2219 2232 25319825 PMC4201284
- Riley P Anson-Cartwright L Cross JC 1998 The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis Nature genetics 18 271 275 9500551
- Roberts JM Taylor RN Musci TJ Rodgers GM Hubel CA McLaughlin MK 1989 Preeclampsia: an endothelial cell disorder American journal of obstetrics and gynecology 161 1200 1204 2589440
- Rossant J Cross JC 2001 Placental development: lessons from mouse mutants Nature reviews Genetics 2 538 548 11433360
- Rossant J Tam PP 2009 Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse Development 136 701 713 19201946
- Scott IC Anson-Cartwright L Riley P Reda D Cross JC 2000 The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms Molecular and cellular biology 20 530 541 10611232 PMC85124
- Simister NE Story CM 1997 Human placental Fc receptors and the transmission of antibodies from mother to fetus Journal of reproductive immunology 37 1 23 9501287
- Smith CM Finger JH Hayamizu TF McCright IJ Xu J Berghout J Campbell J Corbani LE Forthofer KL Frost PJ 2014 The mouse Gene Expression Database (GXD): 2014 update Nucleic acids research 42 D818 824 24163257 PMC3965015
- Strumpf D Mao CA Yamanaka Y Ralston A Chawengsaksophak K Beck F Rossant J 2005 Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst Development 132 2093 2102 15788452
- Suzuki S 2008 Clinical significance of pregnancies with circumvallate placenta The journal of obstetrics and gynaecology research 34 51 54 18226129
- Tanaka S Kunath T Hadjantonakis AK Nagy A Rossant J 1998 Promotion of trophoblast stem cell proliferation by FGF4 Science 282 2072 2075 9851926
- Waite LL Person EC Zhou Y Lim KH Scanlan TS Taylor RN 2000 Placental peroxisome proliferator-activated receptor-gamma is up-regulated by pregnancy serum The Journal of clinical endocrinology and metabolism 85 3808 3814 11061543
- Webb CF Bryant J Popowski M Allred L Kim D Harriss J Schmidt C Miner CA Rose K Cheng HL 2011 The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development Molecular and cellular biology 31 1041 1053 21199920 PMC3067827
- Xu RH Chen X Li DS Li R Addicks GC Glennon C Zwaka TP Thomson JA 2002 BMP4 initiates human embryonic stem cell differentiation to trophoblast Nature biotechnology 20 1261 1264 12426580
- Zeisler H Hund M Verlohren S 2016 The sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia The New England journal of medicine 374 1785 1786 27144854
- Zernicka-Goetz M 2004 First cell fate decisions and spatial patterning in the early mouse embryo Seminars in cell & developmental biology 15 563 572 15271302
Cited by
Sorted by citations
Cheng, C. C. Y., Cheung, M. F., Lee, A. Y., Wu, Q., Chow, S. H.-C., Ang, J. Y. J., Riquelme Medina, I., Lo, G., Wu, H., Yang, W., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09154-w · Cited by 3 · see citing works
- Authors
- Rhee, C., Edwards, M., Dang, C., Harris, J., Brown, M., Kim, J., & Tucker, H. O.
- Affiliations
- The University of Texas at Austin (US)
- Colorado State University (US)
- Corresponding author
- Tucker, Haley O.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 422
- Issue
- 2
- Pages
- 83-91
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC5540318
- OpenAlex
- W2559881236
- Cited by
- 42
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 6
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01GM112722, R01CA31534)
- CPRIT (RP120348, RP120459)
- Marie Betzner Morrow Centennial Endowment
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- ARID3A, placental development, trophoblast giant cells, trophoblast differentiation, trophectoderm, BMP4, induced pluripotent stem cells, placental inflammation, fetal growth restriction, nuclear translocation
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Female, Humans, Mice, Inbred C57BL, Morphogenesis, Placenta, Placentation, Pregnancy, Transcription Factors, Trophoblasts, Giant Cells, Cytokines, Mice, Knockout, Gene Expression Regulation, Developmental, Active Transport, Cell Nucleus, Mice, Bone Morphogenetic Protein 4, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review