ArticleiScience2023
Restricting genomic actions of innate immune mediators on fetal hematopoietic progenitor cells.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- GATA2 decommissioning of enhancers: A mechanism to constrain inflammatory signaling.Cell reports · 2025Article
- GATA2 mutation is associated with immune dysfunction and increased Mycobacterium haemophilum susceptibility in immunocompromised individuals.JCI insight · 2025Article
- Dual mechanism of inflammation sensing by the hematopoietic progenitor genome.Science advances · 2025Article
- BmNPV interacts with super-enhancer regions of the host chromatin to hijack cellular transcription machinery.Nucleic acids research · 2025Article
- Article
- Pathogenic GATA2 genetic variants utilize an obligate enhancer mechanism to distort a multilineage differentiation program.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gata2 noncoding genetic variation as a determinant of hematopoietic stem/progenitor cell mobilization efficiency.Blood advances · 2023Article
- A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice.The Journal of clinical investigation · 2023Article
- A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process.Nature communications · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Innate immune signaling protects against pathogens, controls hematopoietic development, and functions in oncogenesis, yet the relationship between these mechanisms is undefined. Downregulating the GATA2 transcription factor in fetal hematopoietic progenitor cells upregulates genes encoding innate immune regulators, increases Interferon-γ (IFNγ) signaling, and disrupts differentiation. We demonstrate that deletion of an enhancer that confers GATA2 expression in fetal progenitors elevated Toll-like receptor (TLR) TLR1/2 and TLR2/6 expression and signaling. Rescue by expressing GATA2 downregulated elevated TLR signaling. IFNγ amplified TLR1/2 and TLR2/6 signaling in GATA2-deficient progenitors, synergistically activating cytokine/chemokine genes and elevating cytokine/chemokine production in myeloid cell progeny. Genomic analysis of how innate immune signaling remodels the GATA2-deficient progenitor transcriptome revealed hypersensitive responses at innate immune genes harboring motifs for signal-dependent transcription factors and factors not linked to these mechanisms. As GATA2 establishes a transcriptome that constrains innate immune signaling, insufficient GATA2 renders fetal progenitor cells hypersensitive to innate immune signaling.
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What Socratic holds
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 Socratic graph.