ArticlePloS one2014
Granulopoiesis requires increased C/EBPα compared to monopoiesis, correlated with elevated Cebpa in immature G-CSF receptor versus M-CSF receptor expressing cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- SCOPE: Localizing fate-decision states and their regulatory drivers in single-cell differentiation.bioRxiv : the preprint server for biology · 2026Article
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- A JAGN1-associated severe congenital neutropenia zebrafish model revealed an altered G-CSFR signaling and UPR activation.Blood advances · 2024Article
- From Genotype to Phenotype: How Enhancers Control Gene Expression and Cell Identity in Hematopoiesis.HemaSphere · 2023Review
- Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multiomics.Nature methods · 2023Article
- Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity.eLife · 2023Article
- RUNX1::ETO translocations must precede CSF3R mutations to promote acute myeloid leukemia development.Leukemia · 2023Article
- Review
- A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer.Frontiers in oncology · 2022Review
- Data-driven modeling predicts gene regulatory network dynamics during the differentiation of multipotential hematopoietic progenitors.PLoS computational biology · 2022Article
- Trib1 regulates T cell differentiation during chronic infection by restraining the effector program.The Journal of experimental medicine · 2020Article
- Transcription factor and cytokine regulation of eosinophil lineage commitment.Current opinion in hematology · 2020Review
- Trib1 regulates eosinophil lineage commitment and identity by restraining the neutrophil program.Blood · 2019Article
- Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Paralogs of Common Carp Granulocyte Colony-Stimulating Factor (G-CSF) Have Different Functions Regarding Development, Trafficking and Activation of Neutrophils.Frontiers in immunology · 2019Article
- MAPK p38alpha Kinase Influences Haematopoiesis in Embryonic Stem Cells.Stem cells international · 2019Article
- The Endless Saga of Monocyte Diversity.Frontiers in immunology · 2019Review
- Long Non-coding RNAs in Myeloid Malignancies.Frontiers in oncology · 2019Review
- The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis.Microbiology and molecular biology reviews : MMBR · 2018Review
- Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cells.Frontiers in immunology · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
C/EBPα is required for the formation of granulocyte-monocyte progenitors; however, its role in subsequent myeloid lineage specification remains uncertain. Transduction of murine marrow with either of two Cebpa shRNAs markedly increases monocyte and reduces granulocyte colonies in methylcellulose or the monocyte to neutrophil ratio in liquid culture. Similar findings were found after marrow shRNA transduction and transplantation and with CEBPA knockdown in human marrow CD34+ cells. These results apparently reflect altered myeloid lineage specification, as similar knockdown allowed nearly complete 32Dcl3 granulocytic maturation. Cebpa knockdown also generated lineage-negative blasts with increased colony replating capacity but unchanged cell cycle parameters, likely reflecting complete differentiation block. The shRNA having the greatest effect on lineage skewing reduced Cebpa 3-fold in differentiating cells but 6-fold in accumulating blasts. Indicating that Cebpa is the relevant shRNA target, shRNA-resistant C/EBPα-ER rescued marrow myelopoiesis. Cebpa knockdown in murine marrow cells also increased in vitro erythropoiesis, perhaps reflecting 1.6-fold reduction in PU.1 leading to GATA-1 derepression. Global gene expression analysis of lineage-negative blasts that accumulate after Cebpa knockdown demonstrated reduction in Cebpe and Gfi1, known transcriptional regulators of granulopoiesis, and also reduced Ets1 and Klf5. Populations enriched for immature granulocyte or monocyte progenitor/precursors were isolated by sorting Lin-Sca-1-c-Kit+ cells into GCSFR+MCSFR- or GCSFR-MCSFR+ subsets. Cebpa, Cebpe, Gfi1, Ets1, and Klf5 RNAs were increased in the c-Kit+GCSFR+ and Klf4 and Irf8 in the c-Kit+MCSFR+ populations, with PU.1 levels similar in both. In summary, higher levels of C/EBPα are required for granulocyte and lower levels for monocyte lineage specification, and this myeloid bifurcation may be facilitated by increased Cebpa gene expression in granulocyte compared with monocyte progenitors.
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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.