ArticleProceedings of the National Academy of Sciences of the United States of America2021
MSX2 safeguards syncytiotrophoblast fate of human trophoblast stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.Human reproduction update · 2024Pooled it
- Gene regulation at the early human maternal-fetal interface.Nature reviews. Genetics · 2026Review
- CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Roles of Msx2 in exogen control: modulating the stem cell niche during the transition from hair shedding to regeneration.Journal of advanced research · 2026Article
- Reduced FBXO22 skews human trophoblast fate equilibrium toward syncytialization via polyubiquitinating the CoREST complex.Nucleic acids research · 2026Article
- Functional heterogeneity in trophoblast stem cells derived from recurrent pregnancy loss products of conception.Molecular human reproduction · 2026Article
- Activity of the SWI/SNF complex is indispensable for syncytiotrophoblast formation.Development (Cambridge, England) · 2025Article
- BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The homeobox transcription factor MNX1 regulates the expression of many non-MN-specific neuronal genes in motor neurons.Nucleic acids research · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- Two classes of syncytiotrophoblast nuclei form following BAP-driven human pluripotent stem cell differentiation.Placenta · 2025Article
- PPARG-centric transcriptional re-wiring during differentiation of human trophoblast stem cells into extravillous trophoblasts.Nucleic acids research · 2025Article
- Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells.Communications biology · 2025Article
- Eomesodermin in conjunction with the BAF complex promotes expansion and invasion of the trophectoderm lineage.Nature communications · 2025Article
- Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025Review
- Review
- Retinoic acid drives surface epithelium fate determination through the TCF7-MSX2 axis.Cellular and molecular life sciences : CMLS · 2024Article
- Spatial multiomic landscape of the human placenta at molecular resolution.Nature medicine · 2024Article
- Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.Biomolecules · 2024Article
- METTL3 shapes m6A epitranscriptomic landscape for successful human placentation.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple placental pathologies are associated with failures in trophoblast differentiation, yet the underlying transcriptional regulation is poorly understood. Here, we discovered msh homeobox 2 (MSX2) as a key transcriptional regulator of trophoblast identity using the human trophoblast stem cell model. Depletion of MSX2 resulted in activation of the syncytiotrophoblast transcriptional program, while forced expression of MSX2 blocked it. We demonstrated that a large proportion of the affected genes were directly bound and regulated by MSX2 and identified components of the SWItch/Sucrose nonfermentable (SWI/SNF) complex as strong MSX2 interactors and target gene cobinders. MSX2 cooperated specifically with the SWI/SNF canonical BAF (cBAF) subcomplex and cooccupied, together with H3K27ac, a number of differentiation genes. Increased H3K27ac and cBAF occupancy upon MSX2 depletion imply that MSX2 prevents premature syncytiotrophoblast differentiation. Our findings established MSX2 as a repressor of the syncytiotrophoblast lineage and demonstrated its pivotal role in cell fate decisions that govern human placental development and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.