ArticleGenome biology2018
Alternative splicing links histone modifications to stem cell fate decision.
Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing.Genome research · 2025Pooled it
- Histone Modifications in Psychiatry: From Canonical Marks to Neurotransmitter-Mediated Epigenetic Signatures.Alpha psychiatry · 2026Review
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- Splicing retention and enhancer divergence govern the evolutionary fate of ohnologues following whole-genome duplication in rainbow trout.Scientific reports · 2026Article
- Improving gene isoform quantification with miniQuant.Nature biotechnology · 2026Article
- RNA-binding proteins connect Exon usage to the chromatin.NAR genomics and bioinformatics · 2025Article
- Sex-biased transcriptome in in vitro produced bovine early embryos.Cell & bioscience · 2025Article
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.Molecular cell · 2025Article
- LincRNA-ASAO promotes dental pulp repair through interacting with PTBP1 to increase ALPL alternative splicing.Stem cell research & therapy · 2025Article
- The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.Cancers · 2024Review
- Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker.Clinical and translational medicine · 2024Article
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.bioRxiv : the preprint server for biology · 2024Article
- Single-cell analysis of isoform switching and transposable element expression during preimplantation embryonic development.PLoS biology · 2024Article
- Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.PloS one · 2024Article
- Analysis of alternative splicing in chicken macrophages infected with avian pathogenicAnimal biotechnology · 2023Article
- Molecular Mechanisms of Lupus Susceptibility Allele PBX1D.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Single-cell and long-read sequencing to enhance modelling of splicing and cell-fate determination.Computational and structural biotechnology journal · 2023Review
- Research progress of PBX1 in developmental and regenerative medicine.International journal of medical sciences · 2023Review
- Locus-Specific Isolation of theInternational journal of molecular sciences · 2022Article
- The emerging significance of splicing in vertebrate development.Development (Cambridge, England) · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundUnderstanding the embryonic stem cell (ESC) fate decision between self-renewal and proper differentiation is important for developmental biology and regenerative medicine. Attention has focused on mechanisms involving histone modifications, alternative pre-messenger RNA splicing, and cell-cycle progression. However, their intricate interrelations and joint contributions to ESC fate decision remain unclear.
resultsWe analyze the transcriptomes and epigenomes of human ESC and five types of differentiated cells. We identify thousands of alternatively spliced exons and reveal their development and lineage-dependent characterizations. Several histone modifications show dynamic changes in alternatively spliced exons and three are strongly associated with 52.8% of alternative splicing events upon hESC differentiation. The histone modification-associated alternatively spliced genes predominantly function in G2/M phases and ATM/ATR-mediated DNA damage response pathway for cell differentiation, whereas other alternatively spliced genes are enriched in the G1 phase and pathways for self-renewal. These results imply a potential epigenetic mechanism by which some histone modifications contribute to ESC fate decision through the regulation of alternative splicing in specific pathways and cell-cycle genes. Supported by experimental validations and extended datasets from Roadmap/ENCODE projects, we exemplify this mechanism by a cell-cycle-related transcription factor, PBX1, which regulates the pluripotency regulatory network by binding to NANOG. We suggest that the isoform switch from PBX1a to PBX1b links H3K36me3 to hESC fate determination through the PSIP1/SRSF1 adaptor, which results in the exon skipping of PBX1.
conclusionWe reveal the mechanism by which alternative splicing links histone modifications to stem cell fate decision.
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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.