ArticleCell stem cell2022
Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity.
Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Hematopoietic Stem Cell Metabolism during Stress and Aging.Advances in geriatric medicine and research · 2026Article
- Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia.Nature communications · 2026Article
- Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.Science advances · 2026Article
- MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2.Leukemia · 2026Article
- Pathological transcriptional retention of Cyp26b1 in perirenal adipose-derived stem cells contributes to MASLD progression.Hepatology international · 2026Article
- Article
- Serotype-specific effects of adenovirus 5 and 52 E4ORF1 proteins on endothelial cell-mediated regulation of hematopoietic stem cell expansion and lineage differentiation.In vitro cellular & developmental biology. Animal · 2026Article
- Metabolic and epigenetic interplay in HSPC specification: A balance between extrinsic and intrinsic cues.iScience · 2026Review
- Intrinsic and niche-dependent metabolic regulation of haematopoietic stem cells and implications for leukaemogenesis.Nature cell biology · 2026Review
- Lack of MDA5 delays hematopoietic aging by modulating inflammaging and proteostasis in mice.Nature communications · 2026Article
- Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging.The Journal of experimental medicine · 2026Article
- Article
- Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation.Cell reports · 2025Article
- Differentiation latency and dormancy signatures define fetal liver hematopoietic stem cells at single-cell resolution.Cell reports · 2025Article
- High-Risk neuroblastoma therapeutics Topotecan and 13-cis-Retinoic acid modulate autophagy and induce DNA damage response in hematopoietic stem cells and monocytes.Scientific reports · 2025Article
- Metabolism and HSC fate: what NADPH is made for.Trends in cell biology · 2025Review
- Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging.Cell stem cell · 2025Article
- Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells.Nature cell biology · 2025Article
- Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment.HemaSphere · 2025Review
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Hematopoietic stem cells (HSCs) rely on complex regulatory networks to preserve stemness. Due to the scarcity of HSCs, technical challenges have limited our insights into the interplay between metabolites, transcription, and the epigenome. In this study, we generated low-input metabolomics, transcriptomics, chromatin accessibility, and chromatin immunoprecipitation data, revealing distinct metabolic hubs that are enriched in HSCs and their downstream multipotent progenitors. Mechanistically, we uncover a non-classical retinoic acid (RA) signaling axis that regulates HSC function. We show that HSCs rely on Cyp26b1, an enzyme conventionally considered to limit RA effects in the cell. In contrast to the traditional view, we demonstrate that Cyp26b1 is indispensable for production of the active metabolite 4-oxo-RA. Further, RA receptor beta (Rarb) is required for complete transmission of 4-oxo-RA-mediated signaling to maintain stem cells. Our findings emphasize that a single metabolite controls stem cell fate by instructing epigenetic and transcriptional attributes.
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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.