ArticleThe Journal of clinical investigation2021
Zeb1 modulates hematopoietic stem cell fates required for suppressing acute myeloid leukemia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- ZEB1 drives terminal erythroid maturation by controlling the GATA2-KLF1 regulatory switch.Nucleic acids research · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Article
- Impaired DNA damage responses and inflammatory signaling underpin hematopoietic stem cell defects in Gata2 haploinsufficiency.Stem cell reports · 2025Article
- A heterozygous CEBPA mutation disrupting the bZIP domain in a RUNX1 and SRSF2 mutational background causes MDS disease progression.Nature communications · 2025Article
- Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures.BMC genomics · 2025Article
- Dualistic role of ZEB1 and ZEB2 in tumor progression.Biology direct · 2025Review
- Review
- ZEB1 Inhibits LHβ Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice.Endocrinology · 2024Article
- The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.Biomedicines · 2024Review
- Corneal injury repair and the potential involvement of ZEB1.Eye and vision (London, England) · 2024Review
- Conditional deletion of Zeb1 in Csf1riScience · 2024Article
- Article
- The landscape of SETBP1 gene expression and transcription factor activity across human tissues.PloS one · 2024Article
- Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.Frontiers in pharmacology · 2024Review
- Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9Haematologica · 2024Article
- Isolation of tumor stem-like cells from primary laryngeal squamous cell carcinoma cells (FD-LS-6).Human cell · 2024Article
- Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1.Molecular oncology · 2023Article
- A Vaccine against Cancer: Can There Be a Possible Strategy to Face the Challenge? Possible Targets and Paradoxical Effects.Vaccines · 2023Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal transition (EMT) transcription factor, confers properties of "stemness," such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system as a well-established paradigm of stem cell biology to evaluate Zeb1-mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knock out (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid-onset thymic atrophy and apoptosis-driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multilineage differentiation block were observed in Zeb1-KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multilineage differentiation genes and of cell polarity consisting of cytoskeleton-, lipid metabolism/lipid membrane-, and cell adhesion-related genes. Notably, epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1-KO HSCs, which correlated with enhanced cell survival, diminished mitochondrial metabolism, ribosome biogenesis, and differentiation capacity and an activated transcriptomic signature associated with acute myeloid leukemia (AML) signaling. ZEB1 expression was downregulated in AML patients, and Zeb1 KO in the malignant counterparts of HSCs - leukemic stem cells (LSCs) - accelerated MLL-AF9- and Meis1a/Hoxa9-driven AML progression, implicating Zeb1 as a tumor suppressor in AML LSCs. Thus, Zeb1 acts as a transcriptional regulator in hematopoiesis, critically coordinating HSC self-renewal, apoptotic, and multilineage differentiation fates required to suppress leukemic potential in AML.
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