ArticleNature communications2022
Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content.
Article in Nature communications, 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 60 papers.
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Who cites it
60 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Metformin improves chronic rhinosinusitis with depressive-like behavior in mice by targeting TCF4 to inhibit the TLR4/NF-κB pathway.Scientific reports · 2026Article
- Single-cell multi-omic analyses resolve the cellular diversity of ALK/ROS1/MET/NTRK-fused gliomas in infants and older children.bioRxiv : the preprint server for biology · 2026Article
- A gene therapy strategy for Deoxyhypusine Synthase (DHPS) syndrome.Research square · 2026Article
- Transcription Factors in the Pathogenesis of Schizophrenia.Life (Basel, Switzerland) · 2026Review
- Super-enhancer-driven TCF4 orchestrates neuroblastoma metastasis by sphingolipid-dependent membrane remodeling and ITGB1-FAK activation.Neuro-oncology · 2026Article
- Probing neuropsychiatric disorders through in vivo CRISPR screening.Current opinion in genetics & development · 2026Review
- TCF4 at the crest of development: a zebrafish model to explore craniofacial and gastrointestinal defects in Pitt-Hopkins syndrome.Frontiers in cell and developmental biology · 2026Article
- Selective enrichment of TCF4 in GABAergic neurons during postnatal primate development.Frontiers in neuroanatomy · 2026Article
- Assessing the effects of methylphenidate in proliferation and Wnt activity of neuronal stem cells from attention deficit/hyperactivity disorder patients.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients.Neuroscience applied · 2026Article
- Juvenile reinstatement of TCF4 in Pitt-Hopkins syndrome model mice reveals a critical window for genetic intervention.bioRxiv : the preprint server for biology · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- INSM1 governs a neuronal progenitor state that drives glioblastoma in a human stem cell model.Nature communications · 2025Article
- Graphene-polymer nanofibers enable optically induced electrical responses in stem cell-derived electrically excitable cells and brain organoids.Biomaterials · 2025Article
- Sensory abnormalities in autism spectrum disorder and their in vitro modeling.Translational psychiatry · 2025Review
- Decomposing genetic effects of social connectedness and depression on youth behaviors and long-term clinical outcomes.medRxiv : the preprint server for health sciences · 2025Article
- Large-scale discovery of neural enhancers for cis-regulation therapies.bioRxiv : the preprint server for biology · 2025Article
- Impact of intermittent lead exposure on hominid brain evolution.Science advances · 2025Article
- Molecular and developmental deficits in Smith-Magenis syndrome human stem cell-derived cortical neural models.American journal of human genetics · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.
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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.