ArticleProceedings of the National Academy of Sciences of the United States of America2018
Screening for genes that regulate the differentiation of human megakaryocytic lineage cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Generation and single-cell characterization of functional megakaryocytes derived from umbilical cord blood.Stem cell research & therapy · 2026Article
- Dietary restriction mitigates 5-fluorouracil-induced thrombocytopenia in aged mice via mitochondrial potentiation in hematopoietic stem cells and megakaryocyte progenitors.Stem cell reports · 2026Article
- Efficient Generation of Megakaryocyte Progenitors and Platelets From HSPCs via JAK2/STAT3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- BRD9 regulates normal human hematopoietic stem cell function and lineage differentiation.Cell death and differentiation · 2024Article
- Expansion of Human Megakaryocyte-Lineage Progeny via Aryl Hydrocarbon Receptor Antagonism with CH223191.Stem cell reviews and reports · 2022Article
- Inference of cell state transitions and cell fate plasticity from single-cell with MARGARET.Nucleic acids research · 2022Article
- Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- SAHA Enhances Differentiation of CD34+CD45+ Hematopoietic Stem and Progenitor Cells from Pluripotent Stem Cells Concomitant with an Increase in Hemogenic Endothelium.Stem cells translational medicine · 2022Article
- Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells.Science advances · 2022Article
- Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells.Stem cell research & therapy · 2022Article
- Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia.Frontiers in immunology · 2022Article
- The Y14-p53 regulatory circuit in megakaryocyte differentiation and thrombocytopenia.iScience · 2021Article
- Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells.Stem cell reports · 2021Article
- CRISPR-edited megakaryocytes for rapid screening of platelet gene functions.Blood advances · 2021Article
- Review
- Lung megakaryocytes display distinct transcriptional and phenotypic properties.Blood advances · 2020Article
- N-Methyl-D-Aspartate Receptor Hypofunction in Meg-01 Cells Reveals a Role for Intracellular Calcium Homeostasis in Balancing Megakaryocytic-Erythroid Differentiation.Thrombosis and haemostasis · 2020Article
- The GABA receptor GABRR1 is expressed on and functional in hematopoietic stem cells and megakaryocyte progenitors.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- New Insights Into the Differentiation of Megakaryocytes From Hematopoietic Progenitors.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Hunting for hematopoietic transcriptional networks.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
Different combinations of transcription factors (TFs) function at each stage of hematopoiesis, leading to distinct expression patterns of lineage-specific genes. The identification of such regulators and their functions in hematopoiesis remain largely unresolved. In this study, we utilized screening approaches to study the transcriptional regulators of megakaryocyte progenitor (MkP) generation, a key step before platelet production. Promising candidate genes were generated from a microarray platform gene expression commons and individually manipulated in human hematopoietic stem and progenitor cells (HSPCs). Deletion of some of the candidate genes (the hit genes) by CRISPR/Cas9 led to decreased MkP generation during HSPC differentiation, while more MkPs were produced when some hit genes were overexpressed in HSPCs. We then demonstrated that overexpression of these genes can increase the frequency of mature megakaryocytic colonies by functional colony forming unit-megakaryocyte (CFU-Mk) assay and the release of platelets after in vitro maturation. Finally, we showed that the histone deacetylase inhibitors could also increase MkP differentiation, possibly by regulating some of the newly identified TFs. Therefore, identification of such regulators will advance the understanding of basic mechanisms of HSPC differentiation and conceivably enable the generation and maturation of megakaryocytes and platelets in vitro.
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