ArticleBlood2015
ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior.Molecular psychiatry · 2026Article
- Transcriptional readthrough at Atf4 locus suppresses Rps19bp1 and impairs heart development.Cardiovascular research · 2026Article
- Faecalibaculum rodentium Alleviates Ionizing Radiation-Induced Damage in Mice by Improving Intestinal Integrity and Hematopoiesis via Its Metabolite Butyrate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Unfolded protein response signaling promotes myeloid cell production and cooperates with oncogenic mutation.bioRxiv : the preprint server for biology · 2025Article
- Transcriptional Readthrough atbioRxiv : the preprint server for biology · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Widespread presence of bone marrow-like hematopoietic stem cell niche in invertebrate skeletons.Science advances · 2025Article
- Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression.iScience · 2025Article
- Metabolic and stress response adaptations in T cells to fever and physiological heat.Trends in immunology · 2025Review
- Cancer ATF4-mediated CD58 endocytosis impairs anti-tumor immunity and immunotherapy.Journal of translational medicine · 2025Article
- The role of the haematopoietic stem cell niche in development and ageing.Nature reviews. Molecular cell biology · 2025Review
- Context matters: role of ATF4 in hematopoiesis.Blood · 2024Article
- Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq.Genome biology · 2024Article
- The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024Review
- Unfolded protein responses in T cell immunity.Frontiers in immunology · 2024Review
- Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence.International journal of molecular sciences · 2023Review
- Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease.JCI insight · 2023Article
- The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Hematopoietic Jagged1 is a fetal liver niche factor required for functional maturation and engraftment of fetal hematopoietic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fetal liver (FL) serves as a predominant site for expansion of functional hematopoietic stem cells (HSCs) during mouse embryogenesis. However, the mechanisms for HSC development in FL remain poorly understood. In this study, we demonstrate that deletion of activating transcription factor 4 (ATF4) significantly impaired hematopoietic development and reduced HSC self-renewal in FL. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region was not affected. The migration activity of ATF4(-/-) HSCs was moderately reduced. Interestingly, the HSC-supporting ability of both endothelial and stromal cells in FL was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed downregulated expression of a panel of cytokines in ATF4(-/-) stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor A (VEGFA). Addition of Angptl3, but not VEGFA, partially rescued the repopulating defect of ATF4(-/-) HSCs in the culture. Furthermore, chromatin immunoprecipitation assay in conjunction with silencing RNA-mediated silencing and complementary DNA overexpression showed transcriptional control of Angptl3 by ATF4. To summarize, ATF4 plays a pivotal role in functional expansion and repopulating efficiency of HSCs in developing FL, and it acts through upregulating transcription of cytokines such as Angptl3 in the microenvironment.
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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.