Downregulation of ZBTB7A/LRF increases fetal hemoglobin expression in β0-thalassemia/hemoglobin E erythroid cells
Issued Date
2025-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105025231463
Pubmed ID
41345769
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025)
Suggested Citation
Chumchuen S., Pornsukjantra T., Innachai P., Khamphikham P., Wongborisuth C., Anurathapan U., Songdej D., Sripichai O., Tangprasittipap A., Hongeng S. Downregulation of ZBTB7A/LRF increases fetal hemoglobin expression in β0-thalassemia/hemoglobin E erythroid cells. Scientific Reports Vol.15 No.1 (2025). doi:10.1038/s41598-025-30762-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113694
Title
Downregulation of ZBTB7A/LRF increases fetal hemoglobin expression in β0-thalassemia/hemoglobin E erythroid cells
Corresponding Author(s)
Other Contributor(s)
Abstract
Zinc finger and BTB domain-containing 7A (ZBTB7A) is a transcription factor repressor of fetal hemoglobin (HbF; α<inf>2</inf>γ<inf>2</inf>) in erythroid cells. Reactivating γ-globin expression represents a promising therapeutic strategy for β-hemoglobinopathies, including β-thalassemia. While ZBTB7A knockdown is known to elevate HbF levels in HUDEP-2 erythroid cell line and human hematopoietic stem/progenitor cell (HSPC)-derived erythroblasts, its effects in patient-derived cells remain less defined. This study investigates the effects of ZBTB7A downregulation in erythroid cells derived from both β<sup>0</sup> thalassemia/hemoglobin E (β<sup>0</sup>-thal/HbE) patients and healthy donors. ZBTB7A knockdown upregulated embryonic and fetal globin genes (ε-, ζ-, γ-globin), and robust HbF induction while suppressing adult globin gene expression (α-, β-, δ-globin) in both groups. Notably, partial ZBTB7A inhibition was sufficient to achieve HbF reactivation. ZBTB7A depletion delayed erythroid maturation in healthy cells, but not in β⁰-thal/HbE cells, revealing a context-dependent effect on differentiation. These findings support ZBTB7A as a compelling target for β-thalassemia therapy, where partial inhibition could potentially offer therapeutic benefit while minimizing adverse effects on erythroid differentiation.