ArticleThe Journal of biological chemistry2015
Fancd2 is required for nuclear retention of Foxo3a in hematopoietic stem cell maintenance.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- miR-29a-3p and TGF-β Axis in Fanconi anemia: mechanisms driving metabolic dysfunction and genome stability.Cellular and molecular life sciences : CMLS · 2025Article
- FOXOs: masters of the equilibrium.The FEBS journal · 2022Review
- Analysis of representative mutants for key DNA repair pathways on healthspan in Caenorhabditis elegans.Mechanisms of ageing and development · 2021Article
- Mitochondria Turnover and Lysosomal Function in Hematopoietic Stem Cell Metabolism.International journal of molecular sciences · 2021Review
- FANCD2 and HES1 suppress inflammation-induced PPARɣ to prevent haematopoietic stem cell exhaustion.British journal of haematology · 2021Article
- Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis.Oxidative medicine and cellular longevity · 2019Review
- The age-regulated zinc finger factor ZNF367 is a new modulator of neuroblast proliferation during embryonic neurogenesis.Scientific reports · 2018Article
- Transcription factors FOXO in the regulation of homeostatic hematopoiesis.Current opinion in hematology · 2018Review
- In Vivo RNAi Screen Unveils PPARγ as a Regulator of Hematopoietic Stem Cell Homeostasis.Stem cell reports · 2017Article
- FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage.The Journal of biological chemistry · 2017Article
- Evidence for AKT-independent regulation of FOXO1 and FOXO3 in haematopoietic stem and progenitor cells.Cell cycle (Georgetown, Tex.) · 2016Article
- FOXO3a & haematopoietic stem cells: Goodbye PI3K, hello SIRT1?Cell cycle (Georgetown, Tex.) · 2016Article
- Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse hematopoietic stem cells.Genomics data · 2015Article
- Advances in the understanding of Fanconi Anemia Complementation Group D2 Protein (FANCD2) in human cancer.Cancer cell & microenvironmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Functional maintenance of hematopoietic stem cells (HSCs) is constantly challenged by stresses like DNA damage and oxidative stress. Here we show that the Fanconi anemia protein Fancd2 and stress transcriptional factor Foxo3a cooperate to prevent HSC exhaustion in mice. Deletion of both Fancd2 and Foxo3a led to an initial expansion followed by a progressive decline of bone marrow stem and progenitor cells. Limiting dilution transplantation and competitive repopulating experiments demonstrated a dramatic reduction of competitive repopulating units and progressive decline in hematopoietic repopulating ability of double-knockout (dKO) HSCs. Analysis of the transcriptome of dKO HSCs revealed perturbation of multiple pathways implicated in HSC exhaustion. Fancd2 deficiency strongly promoted cytoplasmic localization of Foxo3a in HSCs, and re-expression of Fancd2 completely restored nuclear Foxo3a localization. By co-expressing a constitutively active CA-FOXO3a and WT or a nonubiquitinated Fancd2 in dKO bone marrow stem/progenitor cells, we demonstrated that Fancd2 was required for nuclear retention of CA-FOXO3a and for maintaining hematopoietic repopulation of the HSCs. Collectively, these results implicate a functional interaction between the Fanconi anemia DNA repair and FOXO3a pathways in HSC maintenance.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.