ArticleProceedings of the National Academy of Sciences of the United States of America2022
The multifaceted role of GCM1 during trophoblast differentiation in the human placenta.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 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
- Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures.Molecular human reproduction · 2026Article
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.EMBO reports · 2026Article
- Characterizing glial cells missing transcription factor 1 (GCM1)'s role in regulating placental gene expression.Placenta · 2026Article
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- Arginine methyltransferase PRMT1 equipoises trophoblast development to prevent early pregnancy loss.Nature communications · 2026Article
- Placental dysfunction reflects endocrine impairment and trophoblast alterations in polycystic ovarian syndrome.Scientific reports · 2026Article
- Reduced FBXO22 skews human trophoblast fate equilibrium toward syncytialization via polyubiquitinating the CoREST complex.Nucleic acids research · 2026Article
- IGFBP3 repression driven by inflammation links air pollution to placental and developmental defects.EMBO molecular medicine · 2026Article
- Directed differentiation of bovine trophoblast stem cells: A useful in vitro model for placenta development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Trophoblast differentiation in the bovine placenta.The Journal of reproduction and development · 2026Review
- The placental maturation inflection point: an integrative biological framework for understanding early-onset versus late-onset preeclampsia.Frontiers in endocrinology · 2026Review
- Article
- Gcm1 Orchestrates Lef1 Expression in Folate Deficiency-Induced Neural Tube Defects.Molecular neurobiology · 2025Article
- Activity of the SWI/SNF complex is indispensable for syncytiotrophoblast formation.Development (Cambridge, England) · 2025Article
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.bioRxiv : the preprint server for biology · 2025Article
- 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
- Analyzing the relationship of RNA and DNA methylation with gene expression.Genome biology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Remodeling of the uterine vasculature by invasive extravillous trophoblasts (EVTs) is a critical aspect of human placentation. Insufficient EVT invasion can lead to severe obstetrical complications like preeclampsia, intrauterine growth restriction, and preterm birth. Glial cells missing-1 (GCM1) is a transcription factor that is crucial for proper placentation in mice, and is highly expressed in human syncytiotrophoblast (ST) and EVTs. GCM1 is classically considered a master regulator of ST formation, but little is known about its contribution to the development and function of EVTs. Therefore, in this study we test the hypothesis that GCM1 is a critical regulator of both EVT and ST development and function. We show that GCM1 is highly expressed in human trophoblast stem (TS) cells differentiated into either ST or EVTs. Knockdown of GCM1 in TS cells hindered differentiation into both ST and EVT pathways. When placed in ST media, GCM1-knockdown cells formed small, unstable clusters; when placed in EVT media, cells had altered morphology and transcript profiles resembling cells trapped in an intermediate state between CT and EVT, and invasive capacity through matrix was reduced. RNA sequencing analysis of GCM1-deficient TS cells revealed downregulation of EVT-associated genes and enrichment in transcripts related to WNT signaling, which was linked to decreased expression of the EVT master regulator ASCL2 and the WNT antagonist NOTUM. Our findings reveal an essential role of GCM1 during ST and EVT development, and suggest that GCM1 regulates differentiation of human TS cells into EVTs by inducing expression of ASCL2 and NOTUM.
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