ArticleThe Journal of clinical investigation2020
Microphthalmia transcription factor expression contributes to bone marrow failure in Fanconi anemia.
Article in The Journal of clinical investigation, 2020. 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
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
9 citing papers in PubMed, 18 citations in OpenAlex.
- Distinct developmental outcomes in DNA repair-deficient FANCC c.67delG mutant and FANCCCell death and differentiation · 2025Article
- Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia.The Journal of experimental medicine · 2025Article
- Contribution of p53-dependent and -independent mechanisms to upregulation of p21 in Fanconi anemia.PLoS genetics · 2024Article
- New Insights into the Fanconi Anemia Pathogenesis: A Crosstalk Between Inflammation and Oxidative Stress.International journal of molecular sciences · 2024Review
- Role of the mesenchymal stromal cells in bone marrow failure of Fanconi Anemia patients.Frontiers in cell and developmental biology · 2024Article
- Fanca deficiency is associated with alterations in osteoclastogenesis that are rescued by TNFα.Cell & bioscience · 2023Article
- Global miRNA expression of bone marrow mesenchymal stem/stromal cells derived from Fanconi anemia patients.Human cell · 2022Article
- The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis.Cell & bioscience · 2021Review
- Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis.Science advances · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic stem cell (HSC) attrition is considered the key event underlying progressive BM failure (BMF) in Fanconi anemia (FA), the most frequent inherited BMF disorder in humans. However, despite major advances, how the cellular, biochemical, and molecular alterations reported in FA lead to HSC exhaustion remains poorly understood. Here, we demonstrated in human and mouse cells that loss-of-function of FANCA or FANCC, products of 2 genes affecting more than 80% of FA patients worldwide, is associated with constitutive expression of the transcription factor microphthalmia (MiTF) through the cooperative, unscheduled activation of several stress-signaling pathways, including the SMAD2/3, p38 MAPK, NF-κB, and AKT cascades. We validated the unrestrained Mitf expression downstream of p38 in Fanca-/- mice, which display hallmarks of hematopoietic stress, including loss of HSC quiescence, DNA damage accumulation in HSCs, and reduced HSC repopulation capacity. Importantly, we demonstrated that shRNA-mediated downregulation of Mitf expression or inhibition of p38 signaling rescued HSC quiescence and prevented DNA damage accumulation. Our data support the hypothesis that HSC attrition in FA is the consequence of defects in the DNA-damage response combined with chronic activation of otherwise transiently activated signaling pathways, which jointly prevent the recovery of HSC quiescence.
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.