ArticleGenes & development2014
miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 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
103 citing papers in PubMed, 161 citations in OpenAlex.
- The interplay between non-coding RNAs and Wnt signaling pathway in leukemia: A narrative review.BioImpacts : BI · 2026Review
- miR-302 regulates pancreatic progenitor pool and pancreatic size.Biology open · 2026Article
- Review
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 2025Article
- Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells.Scientific reports · 2025Article
- Review
- Non-coding RNAs mediate mechanical load-regulating bone metabolic homeostasis.Frontiers in cell and developmental biology · 2025Review
- Space radiation damage rescued by inhibition of key spaceflight associated miRNAs.Nature communications · 2024Article
- Genetic and environmental factors driving congenital solitary functioning kidney.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine.Non-coding RNA · 2024Review
- Characterisation of the in-vivo miRNA landscape in Drosophila ribonuclease mutants reveals Pacman-mediated regulation of the highly conserved let-7 cluster during apoptotic processes.Frontiers in genetics · 2024Article
- Identification of Potential miRNA-mRNA Regulatory Network Associated with Growth and Development of Hair Follicles in Forest Musk Deer.Animals : an open access journal from MDPI · 2023Article
- Article
- Insight into microRNAs' involvement in hematopoiesis: current standing point of findings.Stem cell research & therapy · 2023Review
- Malignancy-related mir-210, mir-373 and let-7 levels are affected in iron deficiency anemia.African health sciences · 2023Article
- Notch directs telencephalic development and controls neocortical neuron fate determination by regulating microRNA levels.Development (Cambridge, England) · 2023Article
- RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.Blood · 2023Article
- p53 and HuR combinatorially control the biphasic dynamics of microRNA-125b in response to genotoxic stress.Communications biology · 2023Article
- Article
- Embryonic organizer formation disorder leads to multiorgan dysplasia in Down syndrome.Cell death & disease · 2022Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100∼125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor β (TGFβ) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active β-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFβ signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100∼125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL.
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.