ArticleThe Journal of experimental medicine2013
Sirt1 ablation promotes stress-induced loss of epigenetic and genomic hematopoietic stem and progenitor cell maintenance.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed.
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Regulation of Stem Cell Function by NADPhysiology (Bethesda, Md.) · 2025Review
- scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes.Scientific reports · 2024Article
- Role of SIRT1 in Chemoresistant Leukemia.International journal of molecular sciences · 2023Review
- FOXP1 regulates oxidative stress, SIRT1 expression, and resistance to chemotherapies in acute myeloid leukemia cells.Blood advances · 2023Article
- Ex vivo reprogramming of human hematopoietic stem cells is accompanied by increased transcripts of genes regulating metabolic integrity.Experimental hematology · 2023Article
- A state-of-the-art review on the MicroRNAs roles in hematopoietic stem cell aging and longevity.Cell communication and signaling : CCS · 2023Review
- PBX1-SIRT1 Positive Feedback Loop Attenuates ROS-Mediated HF-MSC Senescence and Apoptosis.Stem cell reviews and reports · 2023Article
- A Therapeutically Targetable NOTCH1-SIRT1-KAT7 Axis in T-cell Leukemia.Blood cancer discovery · 2023Article
- Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia.Communications biology · 2022Article
- Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention.Signal transduction and targeted therapy · 2021Review
- Sirtuins at the Service of Healthy Longevity.Frontiers in physiology · 2021Review
- Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells.Journal of hepatocellular carcinoma · 2021Article
- Aging and leukemic evolution of hematopoietic stem cells under various stress conditions.Inflammation and regeneration · 2020Review
- A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.Cellular and molecular life sciences : CMLS · 2020Review
- Oxidative stress regulates progenitor behavior and cortical neurogenesis.Development (Cambridge, England) · 2020Article
- Lysine acetyltransferase 8 is involved in cerebral development and syndromic intellectual disability.The Journal of clinical investigation · 2020Article
- ATF3 Prevents Stress-Induced Hematopoietic Stem Cell Exhaustion.Frontiers in cell and developmental biology · 2020Article
- Sirtuin 1: A Dilemma in Transplantation.Journal of transplantation · 2020Review
- The Versatility of Sirtuin-1 in Endocrinology and Immunology.Frontiers in cell and developmental biology · 2020Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
The (histone) deacetylase Sirt1 is a mediator of genomic and epigenetic maintenance, both of which are critical aspects of stem cell homeostasis and tightly linked to their functional decline in aging and disease. We show that Sirt1 ablation in adult hematopoietic stem and progenitor cells (HSPCs) promotes aberrant HSPC expansion specifically under conditions of hematopoietic stress, which is associated with genomic instability as well as the accumulation of DNA damage and eventually results in a loss of long-term progenitors. We further demonstrate that progenitor cell expansion is mechanistically linked to the selective up-regulation of the HSPC maintenance factor and polycomb target gene Hoxa9. We show that Sirt1 binds to the Hoxa9 gene, counteracts acetylation of its histone target H4 lysine 16, and in turn promotes polycomb-specific repressive histone modification. Together, these findings demonstrate a dual role for Sirt1 in HSPC homeostasis, both via epigenetic regulation of a key developmental gene and by promoting genome stability in adult stem cells.
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