ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
SCL/TAL1-mediated transcriptional network enhances megakaryocytic specification of human embryonic stem cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Proteomic Validation of MEG-01-Derived Extracellular Vesicles as Representative Models for Megakaryocyte- and Platelet-Derived Extracellular Vesicles.Biomolecules · 2025Article
- Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis.Nature communications · 2025Article
- Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C.Molecular therapy. Nucleic acids · 2023Article
- De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy.Cells · 2023Review
- Functional Evaluation of KEL as an Oncogenic Gene in the Progression of Acute Erythroleukemia.Oxidative medicine and cellular longevity · 2022Article
- Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators.Current genomics · 2019Review
- Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation betweenHaematologica · 2019Article
- A review of connectivity map and computational approaches in pharmacogenomics.Briefings in bioinformatics · 2018Review
- Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells.Blood · 2017Article
- Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.Nature communications · 2016Article
- Lost in translation: pluripotent stem cell-derived hematopoiesis.EMBO molecular medicine · 2015Review
- Article
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12 authors at 3 institutions in 1 country.
Funding
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Abstract
Human embryonic stem cells (hESCs) are a unique in vitro model for studying human developmental biology and represent a potential source for cell replacement strategies. Platelets can be generated from cord blood progenitors and hESCs; however, the molecular mechanisms and determinants controlling the in vitro megakaryocytic specification of hESCs remain elusive. We have recently shown that stem cell leukemia (SCL) overexpression accelerates the emergence of hemato-endothelial progenitors from hESCs and promotes their subsequent differentiation into blood cells with higher clonogenic potential. Given that SCL participates in megakaryocytic commitment, we hypothesized that it may potentiate megakaryopoiesis from hESCs. We show that ectopic SCL expression enhances the emergence of megakaryocytic precursors, mature megakaryocytes (MKs), and platelets in vitro. SCL-overexpressing MKs and platelets respond to different activating stimuli similar to their control counterparts. Gene expression profiling of megakaryocytic precursors shows that SCL overexpression renders a megakaryopoietic molecular signature. Connectivity Map analysis reveals that trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), both histone deacetylase (HDAC) inhibitors, functionally mimic SCL-induced effects. Finally, we confirm that both TSA and SAHA treatment promote the emergence of CD34(+) progenitors, whereas valproic acid, another HDAC inhibitor, potentiates MK and platelet production. We demonstrate that SCL and HDAC inhibitors are megakaryopoiesis regulators in hESCs.
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