ArticleThe Journal of clinical investigation2015
Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis.Antioxidants (Basel, Switzerland) · 2026Review
- Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis.Stem cell reports · 2025Article
- Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential.Nature communications · 2025Article
- A Cell Cycle-Aware Network for Data Integration and Label Transferring of Single-Cell RNA-Seq and ATAC-Seq.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.Advances in experimental medicine and biology · 2024Review
- Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.Genome research · 2023Article
- SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.Stem cells (Dayton, Ohio) · 2023Article
- Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond-Blackfan anemia.Experimental hematology · 2022Article
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- Compounds targeting class II histone deacetylases do not cause panHDACI-associated impairment of megakaryocyte differentiation.Experimental hematology · 2019Article
- GATA6 suppression enhances lung specification from human pluripotent stem cells.The Journal of clinical investigation · 2018Article
- Enhancing functional platelet release in vivo from in vitro-grown megakaryocytes using small molecule inhibitors.Blood advances · 2018Article
- GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: consequences for therapy.Expert review of hematology · 2018Review
- Induced Pluripotent Stem Cell-Derived Megakaryocytes and Platelets for Disease Modeling and Future Clinical Applications.Arteriosclerosis, thrombosis, and vascular biology · 2017Review
- Platelet dense granules begin to selectively accumulate mepacrine during proplatelet formation.Blood advances · 2017Article
- Article
- Development of autologous blood cell therapies.Experimental hematology · 2016Review
- E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells.The Biochemical journal · 2016Article
- Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.Nature communications · 2016Article
- Advances in understanding erythropoiesis: evolving perspectives.British journal of haematology · 2016Review
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Transfusion of donor-derived platelets is commonly used for thrombocytopenia, which results from a variety of clinical conditions and relies on a constant donor supply due to the limited shelf life of these cells. Embryonic stem (ES) and induced pluripotent stem (iPS) cells represent a potential source of megakaryocytes and platelets for transfusion therapies; however, the majority of current ES/iPS cell differentiation protocols are limited by low yields of hematopoietic progeny. In both mice and humans, mutations in the gene-encoding transcription factor GATA1 cause an accumulation of proliferating, developmentally arrested megakaryocytes, suggesting that GATA1 suppression in ES and iPS cell-derived hematopoietic progenitors may enhance megakaryocyte production. Here, we engineered ES cells from WT mice to express a doxycycline-regulated (dox-regulated) shRNA that targets Gata1 transcripts for degradation. Differentiation of these cells in the presence of dox and thrombopoietin (TPO) resulted in an exponential (at least 10¹³-fold) expansion of immature hematopoietic progenitors. Dox withdrawal in combination with multilineage cytokines restored GATA1 expression, resulting in differentiation into erythroblasts and megakaryocytes. Following transfusion into recipient animals, these dox-deprived mature megakaryocytes generated functional platelets. Our findings provide a readily reproducible strategy to exponentially expand ES cell-derived megakaryocyte-erythroid progenitors that have the capacity to differentiate into functional platelet-producing megakaryocytes.
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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.