ArticlePLoS biology2021
Interplay between the EMT transcription factors ZEB1 and ZEB2 regulates hematopoietic stem and progenitor cell differentiation and hematopoietic lineage fidelity.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.Frontiers in oncology · 2024Pooled it
- ZEB1 drives terminal erythroid maturation by controlling the GATA2-KLF1 regulatory switch.Nucleic acids research · 2026Article
- Article
- Transcriptome and experimental validation identify prognostic genes associated with lipotoxicity in thyroid carcinoma.BMC cancer · 2026Article
- Nestin and SOX2 Maintain self-renewal Abilities of Different Pancreatic Cancer Stem Cell Populations.Stem cell reviews and reports · 2026Article
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Review
- ZEB2 Gene Pathogenic Variants Across Protein-Coding Regions and Impact on Clinical Manifestations: A Review.International journal of molecular sciences · 2025Review
- Role of FHOD1 in tumor cells and tumor immune microenvironment.Frontiers in immunology · 2025Review
- The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.Biomedicines · 2024Review
- Conditional deletion of Zeb1 in Csf1riScience · 2024Article
- Epithelial-Mesenchymal Transition in Acute Leukemias.International journal of molecular sciences · 2024Review
- Article
- ALOX5AP is a new prognostic indicator in acute myeloid leukemia.Discover oncology · 2023Article
- Article
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Tumor stemness score to estimate epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) characterization and to predict the prognosis and immunotherapy response in bladder urothelial carcinoma.Stem cell research & therapy · 2023Article
- Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies.Frontiers in oncology · 2023Review
- An "unexpected" role for EMT transcription factors in hematological development and malignancy.Frontiers in immunology · 2023Review
- Zeb1 sustains hematopoietic stem cell functions by suppressing mitofusin-2-mediated mitochondrial fusion.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 5 countries.
Funding
Abstract
The ZEB2 transcription factor has been demonstrated to play important roles in hematopoiesis and leukemic transformation. ZEB1 is a close family member of ZEB2 but has remained more enigmatic concerning its roles in hematopoiesis. Here, we show using conditional loss-of-function approaches and bone marrow (BM) reconstitution experiments that ZEB1 plays a cell-autonomous role in hematopoietic lineage differentiation, particularly as a positive regulator of monocyte development in addition to its previously reported important role in T-cell differentiation. Analysis of existing single-cell (sc) RNA sequencing (RNA-seq) data of early hematopoiesis has revealed distinctive expression differences between Zeb1 and Zeb2 in hematopoietic stem and progenitor cell (HSPC) differentiation, with Zeb2 being more highly and broadly expressed than Zeb1 except at a key transition point (short-term HSC [ST-HSC]➔MPP1), whereby Zeb1 appears to be the dominantly expressed family member. Inducible genetic inactivation of both Zeb1 and Zeb2 using a tamoxifen-inducible Cre-mediated approach leads to acute BM failure at this transition point with increased long-term and short-term hematopoietic stem cell numbers and an accompanying decrease in all hematopoietic lineage differentiation. Bioinformatics analysis of RNA-seq data has revealed that ZEB2 acts predominantly as a transcriptional repressor involved in restraining mature hematopoietic lineage gene expression programs from being expressed too early in HSPCs. ZEB1 appears to fine-tune this repressive role during hematopoiesis to ensure hematopoietic lineage fidelity. Analysis of Rosa26 locus-based transgenic models has revealed that Zeb1 as well as Zeb2 cDNA-based overexpression within the hematopoietic system can drive extramedullary hematopoiesis/splenomegaly and enhance monocyte development. Finally, inactivation of Zeb2 alone or Zeb1/2 together was found to enhance survival in secondary MLL-AF9 acute myeloid leukemia (AML) models attesting to the oncogenic role of ZEB1/2 in AML.
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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.