| RRC ID |
77349
|
| 著者 |
Daniels DE, Ferrer-Vicens I, Hawksworth J, Andrienko TN, Finnie EM, Bretherton NS, Ferguson DCJ, Oliveira ASF, Szeto JA, Wilson MC, Brewin JN, Frayne J.
|
| タイトル |
Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype.
|
| ジャーナル |
Nat Commun
|
| Abstract |
β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human disease cellular model systems for β-thalassemia by gene editing the erythroid line BEL-A, which accurately recapitulate the phenotype of patient erythroid cells. We also develop a high throughput compatible fluorometric-based assay for evaluating severity of disease phenotype and utilize the assay to demonstrate that the lines respond appropriately to verified reagents. We next use the lines to perform extensive analysis of the altered molecular mechanisms in β-thalassemia erythroid cells, revealing upregulation of a wide range of biological pathways and processes along with potential novel targets for therapeutic investigation. Overall, the lines provide a sustainable supply of disease cells as research tools for identifying therapeutic targets and as screening platforms for new drugs and reagents.
|
| 巻・号 |
14(1)
|
| ページ |
6260
|
| 公開日 |
2023-10-6
|
| DOI |
10.1038/s41467-023-41961-9
|
| PII |
10.1038/s41467-023-41961-9
|
| PMID |
37803026
|
| PMC |
PMC10558456
|
| MeSH |
Erythroid Cells
Erythropoiesis / genetics
Humans
Phenotype
beta-Thalassemia* / genetics
beta-Thalassemia* / therapy
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
HUDEP-2(RCB4557) |
