ArticleNature communications2022
Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Gene regulation at the early human maternal-fetal interface.Nature reviews. Genetics · 2026Review
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.EMBO reports · 2026Article
- Patient-specific trophoblast stem cells for placental medicine.Trends in molecular medicine · 2026Review
- Characterizing glial cells missing transcription factor 1 (GCM1)'s role in regulating placental gene expression.Placenta · 2026Article
- Creatine metabolism regulates trophectoderm formation in early mouse embryos via an energy-cytoskeleton-YAP axis.The Journal of biological chemistry · 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
- Creatine kinase regulates energy metabolism and growth of trophoblasts.bioRxiv : the preprint server for biology · 2026Article
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Single-cell insights into trophoblast heterogeneity and adaptive dysfunction in selective fetal growth restriction.Communications biology · 2026Article
- Metabolism and homeostasis of energy in trophoblast cells of the placenta: from development to disease†.Biology of reproduction · 2026Review
- Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.Cell regeneration (London, England) · 2026Article
- Trophoblast Fusion Deficiency in Placenta-Related Pregnancy Disorders.Advances in experimental medicine and biology · 2026Review
- Creatine Kinase Blockade Disrupts Energy Metabolism and Redox Homeostasis to Suppress Osteosarcoma Progression.International journal of molecular sciences · 2025Article
- BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.bioRxiv : the preprint server for biology · 2025Article
- Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells.Communications biology · 2025Article
- Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells.Stem cell reports · 2025Article
- Chorionic trophoblast cells demonstrate functionally different phenotypes from placental trophoblasts†.Biology of reproduction · 2025Article
- A Novel 6-bp Repeat Unit (6-bp RU) of the 13th Intron Within the ConservedInternational journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combination of EGF, CHIR99021, A83-01, SB431542, VPA, and Y27632 (EGF/CASVY) facilitates the derivation of trophoblast stem (TS) cells from human blastocysts and first-trimester, but not term, cytotrophoblasts. The mechanism underlying this chemical induction of TS cells remains elusive. Here we demonstrate that the induction efficiency of cytotrophoblast is determined by functional antagonism of the placental transcription factor GCM1 and the stemness regulator ΔNp63α. ΔNp63α reduces GCM1 transcriptional activity, whereas GCM1 inhibits ΔNp63α oligomerization and autoregulation. EGF/CASVY cocktail activates ΔNp63α, thereby partially inhibiting GCM1 activity and reverting term cytotrophoblasts into stem cells. By applying hypoxia condition, we can further reduce GCM1 activity and successfully induce term cytotrophoblasts into TS cells. Consequently, we identify mitochondrial creatine kinase 1 (CKMT1) as a key GCM1 target crucial for syncytiotrophoblast differentiation and reveal decreased CKMT1 expression in preeclampsia. Our study delineates the molecular underpinnings of trophoblast stemness and differentiation and an efficient method to establish TS cells from term placentas.
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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.