論文 - 詳細
| RRC ID | 89690 |
|---|---|
| 著者 | Zin TN, Jatavan P, Sakunpansap N, Charoenkwan P, Khamphikham P. |
| タイトル | Establishment of an immortalized erythroid model for Hb Bart's hydrops fetalis with homozygous α0-thalassemia Southeast Asian deletion. |
| ジャーナル | Sci Rep |
| Abstract |
Hemoglobin Bart's hydrops fetalis syndrome (BHFS) is the most severe form of α-thalassemia and is highly prevalent in Southeast Asia. It is most commonly caused by homozygosity for the α0-thalassemia Southeast Asian deletion (--SEA/--SEA), which eliminates α-globin production and results in profound fetal anemia. Current management is limited to intrauterine transfusions with only transient benefit, and no pharmacological or gene-based therapies are available. Progress toward therapy has been hampered by the lack of disease-relevant in vitro models. Here, we established Chery-Bart's, an immortalized erythroid progenitor cell line derived from umbilical cord blood CD34+ hematopoietic stem and progenitor cells of a fetus with --SEA/--SEA and βIVS I-1 (G> T)/β using a tetracycline-inducible HPV16 E6/E7 system. Chery-Bart's cells exhibit sustained proliferation beyond the Hayflick limit, stable recovery after cryopreservation, and enrichment in the basophilic erythroblast stage. In vitro erythropoiesis assays showed that the cell line retains key features of the parental cells, including the capacity for erythroid maturation, expression of fetal globin transcripts, and robust production of Hb Bart's (γ4), the hallmark pathological hemoglobin of BHFS. Although Chery-Bart's carries a β-thalassemia mutation, this is unlikely to modify disease severity, as γ-globin predominates in this model. Collectively, Chery-Bart's represents the first durable and disease-specific cellular model of BHFS with --SEA/--SEA genotype. This platform provides a scalable resource for mechanistic studies and preclinical evaluation of therapeutic approaches, including drug discovery, gene therapy, and α-like globin chain induction. Beyond BHFS, Chery-Bart's may also serve as a model for investigating severe α-thalassemia syndromes associated with the --SEA allele, such as deletional and non-deletional HbH disease. |
| 巻・号 | 16(1) |
| 公開日 | 2026-5-20 |
| DOI | 10.1038/s41598-026-54128-5 |
| PII | 10.1038/s41598-026-54128-5 |
| PMID | 42162272 |
| PMC | PMC13408849 |
| MeSH | Asia, Southeastern Cell Line Erythroid Precursor Cells* / metabolism Erythropoiesis Female Hemoglobins, Abnormal* / genetics Hemoglobins, Abnormal* / metabolism Homozygote Humans Hydrops Fetalis* / genetics Hydrops Fetalis* / pathology Sequence Deletion alpha-Thalassemia* / genetics alpha-Thalassemia* / pathology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 遺伝子材料 | CSIV-TRE-HPV-E6/E7-UbC-KT (RDB17719) |